Effects of chemotherapy on the immunological characteristics of patients with primary destructive pulmonary tuberculosis*

Bulletin ofthe WorldHealth Organization, 62 (5): 763 - 771 (1984) © World HealthOrganization 1984 Effects of chemotherapy on the immunological characteristics of patients with primary destructive pulmonary tuberculosis* A. G. KHOMENKO,1 M. M. AVERBACH,2 V. I. LITVINOV,3 V. J. GERGERT,4 & V. I. CHUKANOVS An investigation of 142 patients with primary destructive pulmonary tuberculosis was carried out using several immunological tests to estimate the quantitative and functional status of the T- and B-lymphocyte systems and the specific cell-mediated and humoral immunity. It was shown that the status of the immune system, and that of the specific antituberculosis immunity in particular, were dependent on the severity of the tuberculosis process. There were indications that the immune status largely determined the extent ofthe infiltrative lesions, as well as the course of the disease. In patients with no pronounced defects in cell-mediated immunity in general and in specific immunity in particular, the time neededfor sputum samples to become bacterially negative andfor the cavities to close was reduced, especially in cases where the initial bacterial excretion was not heavy and the degree ofthe infiltration was not severe. Defects in the immune system impeded the clinical progress ofthe tuberculosispatients; moreover, complete clinical recovery in such cases was delayed and there was a higher incidence of reactivation of the disease during the main chemotherapy course as well as of recurrence of the disease at a later date. In the course of the chemotherapy of tuberculosis, in association with the reduction in the bacterial population (i.e., with the decrease in inflammatory manifestations and the initiation of the reparative process), one can observe changes in immunological parameters; these changes can be correlated with the regression of the tuberculosis process (1-6). The objective of the research project reported here was to examine the immune status of patients with primary destructive pulmonary tuberculosis, before and during treatment, in relation to the progress of the disease. The resolution of infiltration, the closure of cavities, and the disappearance of Mycobacterium tuberculosis from the sputum were taken as reflecting the involution of the tuberculosis process. MATERIALS AND METHODS Patients Clinical and immunological investigations were carried out on 142 patients with destructive * From the Central Institute of Scientific Research in Tubercu- losis, P1. Yauza, Moscow 107564, USSR. ' Director. 2 Deputy Director, and Chief, Laboratory of Experimental Path- ology and Immunology. 3 Chief, Laboratory of Immunochemistry and Immunogenetics. 4 Senior Scientific Staff Associate, Laboratory of Experimental Pathology and Immunology. 5 Senior Scientific Staff Associate, Therapeutical Department. pulmonary tuberculosis. The group under study was composed of 109 male and 33 female patients aged 18-70 years; there were 90 cases of infiltrative and 18 cases of disseminated tuberculosis. The patients were divided into three groups, according to the extent of infiltration and dissemi- nation of disease. Group 1 comprised patients with limited changes and mild infiltration (29 patients); group 2 included patients with well expressed infil- trations, foci of the confluent type and roundish or cloudy infiltrates (72 patients); group 3 comprised patients with extremely pronounced infiltration, lobitis, infiltrative-caseous pneumonia, and extensive confluent disseminations (41 patients). M. tuberculosis was isolated from the sputum and lavage waters of the bronchi of 115 patients, using various techniques. Of these, 78 (67.8%7) were found to be excreting M. tuberculosis in large numbers, i.e., 10 or more mycobacteria per 100 microscopic visual fields and over 20 colonies on the inoculation material; the remaining 37 (32.2%) were producing small numbers of bacilli, i.e., 1-9 mycobacteria in 100 visual fields and 1 or 2 colonies on the inoculation material. Treatment All the patients were hospitalized and given a course of chemotherapy: 69 patients were given isoniazid and rifampicin in combination with either streptomycin, protionamide or ethambutol; 33 4455 -763- A. G. KHOMENKO ET AL. patients were given rifampicin, ethambutol, and protionamide; 40 patients were treated with isoniazid and streptomycin in association with either etham- butol or protionamide. The drugs were taken for 3 months. If the destruction sites healed within this 3- month period, the administration of rifampicin or streptomycin was discontinued, and the patients con- tinued to receive the two remaining drugs. If lesions persisted after the 3-month course, the patients con- tinued to take the three drugs for a total of 6 and, in some cases, 9 months. Immunological techniques The lymphocyte-blast transformation reaction was performed with the lymphocytes of the peripheral blood according to the usual techniques (7). Purified protein derivative of tuberculin (PPD) and phyto- haemagglutinin (PHA) in 199 culture medium were used as the stimulating agents. The cultures with PPD were incubated for 96 hours, and those with PHA for 72 hours. The leukocyte migration inhibition test was carried out with PPD using the capillary method in a Mackaness chamber. The test count was measured after 24 hours of incubation by the ratio of the sizes of the cell migration areas in the chambers with and without PPD. The numbers of T and B lymphocytes in the peri- pheral blood were estimated by means of the E- and EAC-rosette formation tests. The levels of IgG, IgA and IgM antibodies in the sera of the patients were estimated by agar radial immunodiffusion with the antisera against the corres- ponding immunoglobulin class (10). Antituberculin antibodies in the sera were detected by the passive haemagglutination reaction, modified according to Gorina & Olovnikov (11). RESULTS The impact of chemotherapy was assessed in 115 (out of 142) patients with cavities and positive sputum samples, in terms of the time taken for the sputum to become negative and for the cavities to close. It was found that the tuberculosis process took various courses (Table 1). A comparative analysis of the results of the specific immunological and clinical tests displayed a clear-cut correlation between the values of the immunological parameters and treatment efficacy. Thus, the highest values in the blast transformation test with PPD were found in patients whose sputum had become negative and whose cavities had closed. Low values were found in patients with positive sputum and open cavities (Table 2). In the same group, there was a high level of leukocyte migration inhibition with PPD (i.e., low indices were registered) Table 1. Clinical characteristics of tuberculosis patients before and during chemotherapy No. of patients Bacteriological Before Cavities status of 3 months 6 months 9 months sputum treatment - - 0 29 80 105 + - 0 61 29 8 + + 115 25 6 2 Table 2. Results of the lymphocyte-blast transformation reaction with PPD in tuberculosis patients at different stages of chemotherapy Reaction values (%)' Bacteriological BeforeCavities status of 3 months 6 months 9 months sputum treatment - -- 4.99 ± 0.65 5.35 ± 0.35k 5.6 ± 0.29b + - - 3.28 ± 0.27b 2.22 ± 0.23 3.15 ± 0.80 + + 2.01 ±0.1 1.05 ± 0.206 1.27 ± 0.71 0.67 ± 1.19 a Mean ± standard deviation. b Significantly different from other results measured at same time (P < 0.05). 764 IMMUNOLOGICAL CHARACTERISTICS OF TUBERCULOSIS PATIENTS during all stages of the investigation (Table 3). In contrast, disappearance of bacteria from the sputum and closure of the cavities were accompanied by test values approaching 1.0, indicating an almost complete absence of leukocyte migration inhibition. The complete efficacy of the chemotherapy course was also characterized by a reduction in specific anti- body titres (Table 4) after 6 months of treatment. The clinical findings showed that the time taken for discontinuation of excretion of M. tuberculosis was also dependent on the initial level of excretion and the rate of closure of cavities. All the patients excreting low levels of M. tuberculosis were negative by the sixth month, and all cavities in these patients were closed by the ninth month of treatment. On the other hand, in 13% of patients with heavy initial bacterial excretion, the cavities did not close, and 2.6% of patients were still bacteriologically positive 9 months after the start of treatment. As regards the immunological findings, the blast transformation values in the cultures with PPD and the indices of the leukocyte migration-inhibition reaction, both before and during treatment, were lowest in those with a heavy bacterial load (Table 5). The titres of specific antibodies decreased more slowly in the patients with heavier initial bacterial load than in those with mild initial excretion. Table 6 presents the results of the cellular immuno- specific tests according to the time taken for discon- tinuation of bacterial excretion in patients with initial heavy and mild bacterial load. At all stages of the investigation, the values found in the specific blast transformation tests were higher for the patients who became negative within the first 3 months (irres- pective of the initial intensity of bacterial excretion). The same pattern was observed for the results of the leukocyte migration inhibition reaction. Similarly, the results of the blast transformation reaction and the index of the migration inhibition reaction were higher in patients who had early closure of the cavities. Differences in the initial infiltrative changes also influenced the rate of resolution of the infiltrations. Thus, 66.6% of patients in group I (with mild infil- trations) demonstrated resolution of the infiltrations within the first 3 months of treatment; after 6 months, infiltrative inflammatory lesions persisted in only 3.407o of the patients. Conversely, after 3 months of treatment, none of the cases in group 3 demonstrated complete resolution of infiltrations, though some Table 3. Results of the leukocyte migration inhibition reaction with PPD in tuberculosis patients at various stages of chemotherapy Reaction values' Bacteriological Before Cavities status of tre 3 months 6 months 9 months sputum treatment - - - 0.86 + 0.028' 0.902 ± 0.001" 0.92 ± 0.012 + 0.79 + 0.016" 0.77 + 0.028" 0.81 ± 0.08 + + 0.606 0.011 0.61 + 0.031" 0.535 + 0.1 1" 0.69 ± 0.53 a Mean ± standard deviation. b Significantly different from other results measured at same time (P < 0.05). Table 4. Results of the specific passive haemagglutination reaction in the tuberculosis patients at various stages of chemotherapy Reaction values (1092 of the titre)" Bacteriological Before Cavities status of tre 3 months 6 months 9 months sputum treatment 7.72 ± 0.14 6.10 + 0.092" 5.57 + 0.078 + 6.80 + 0.1 1" 6.83 + 0.19 6.25 + 0.53 + + 7.43 + 0.09 7.64 ± 0.21 7.17 ± 0.70 6.50 ± 0.88 a Mean ± standard deviation. h Significantly different from other results measured at same time (P < 0.05). 765 766 A. G. KHOMENKO ET AL. CN C') r~- U) U~~~~~~~~~~~~~~~D'- r-Co o -H -H -H 0 -H -H- -H+E In Le) r- C E OD CD r 007) 0) OD 0 CY) CN 0 00 OD (O ~~~~~~~c.2 COC'I) co C') 4-' 4c- C ~ ~ 0 CO~~~0cCOO CD4c - 0 000D ~~~~~~ E ~~~~~~~~~~~~~~~~~ ~~~~> C 0 WD CV) CO C o 0E0 co6Co 04) (W~~~~~~~~~~~~~C)N1COD-CO >0 C 0 ~~~ E CD N N -~~~~~~~~ ~~~~~~~~~ C ~ C~C) C Nc - ') N 6 m0 0 0 0CC~~~~~~~~~~~ o CD 0 N~~~~-664-' C ~~~~~~~00 C 0 00 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~00 0 EC tDo CD0 CD0 6 4 CU~~~~~~~~~~~~~~~~~~~~~~~~~~~ -4.- 0 CD~ ~~0 '-'0'o .E D6 O '.' 0 -H 1 C~~~~~~E2 0) CD Co 0 . 0) 0 ~~~0) 0 N0 E V C 0 ~~~~~~~ ~~~~C00 0 0 m E~~~C'a0 E20 0 D '-CE ))0 6 6 .2 CV CD0 C > > 0 0(, E - ND 00 0 0 0 D~ 0 C') X) 0 4. & 4.0x~~~~~0Cv4C6 N .00 Coo ~ ~~~~~~~~~~~~~~~~~~~~~~~~~~ '-C 1 0 0CD ~~~~~~~( No E .'0 N- 0 CCX0 0C 6 6 6 000 NCDN-~~~~~~~~C 0004-0~~~~~~~~~ 2 EEC. 0C N-CD CD0- E -0N'00 c'C'4-'- N - N-. . C') D C N .' > ~~~~~~00 0 ~~~~~~~~C)0 0C 01 0 0 0 C. 6 O 6 6 E EE EEU.' - C CX E.E C CD 0) E 4OO ') C'C' C')4C') CD~ ~ 4 C C C14 (0 0 0C.)~+1 -H +1E0 C 0 ~~~~~~~~~~~~~~~~~~~C1 0C00(VE m 0C Cl)~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 04.' 0~~~~~~~~~~~~~~~~~~~~~~~~4 0 C~~~~~~~~~~~~~~~Cc0 C CC C)U) )CU C 0~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~C.00 C.C C 0 0~~~~~~~~~E~~~~~ ~~~~~ ~~~~~0 ~~~~0C 0 CCC 0 C~~~~~~~~~~~~~~~~~~~~~~~~~~~~~00E 0C'r 0 CV CV cV)E co+C0- 0 00Ci ~ ~ 00. Co v-CA0VCQC 2* - 0 0 .C( 0 0. :o .0 C ~~~~~~~ ~~~~~~~~~~~~ 00~~~~~~~~~~~~~~c o_S~~~~~~ ~ ~ ~~ ~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~'0- U00 1r- Co - .-i. IMMUNOLOGICAL CHARACTERISTICS OF TUBERCULOSIS PATIENTS general progress was observed. Even after 6 months, infiltrative inflammations in the lung persisted in 527o of patients in group 3 and after 9 months in 19.5%. In group 2 the infiltrations were found to be healed in 38.807o of cases within 3 months, in 65.27o within 6 months, and in 97.3%o in 9 months. The immunological status of patients with different degrees of infiltrative changes at admission differed in almost all respects characterizing the status of T- cell and B-cell immunity as a whole, and specific immunity in particular. The number of E-rosette forming lymphocytes in the blood was generally lowest in group 3 patients (mean, 39.2 ± 0.9%o); cor- responding levels in patients in groups 1 and 2 were 46.1 ± 1.4q7o and 42.4 ± 0.5%, respectively. The dif- ference between groups 1 and 3 was significant (P < 0.05). The functional activity of the T lymphocytes in the blast transformation test with phytohaemagglutinin was also more suppressed in the patients in group 3 (59.3 ± l.Oo) than in those in group 1 (72.3 ± 1.20%o; P < 0.05). The corresponding indices in the patients in group 2 were intermediate (65.8 ± 0.8%). In contrast, the number of EAC-rosette forming lymphocytes in the peripheral blood was highest in the patients in group 3 (17.6 ± 0.60o). The corresponding value for patients in group 2 was 15.7 ± 0.3%o and for those in group 1, 14.8 ± 0.6%. The difference between the values for the patients in group 1 and group 3 was highly significant (P < 0.001). The values of the E-rosette and EAC-rosette formation test and of the blast transformation reaction with PHA rapidly became normal in the presence of positive clinical development, and did not change much during the later stages of the study, so they are not given here. In the patients in group 1, the values of the blast transformation reaction with PPD were highest at the end of the third month of treat- ment and then decreased slowly until the ninth month. In the patients in group 3, the acceleration of the blast transformation reaction was very slow and did not show a preliminary peak, as seen in group 1. The indices of the leukocyte migration inhibition reaction increased more slowly in the patients in group 3, and only reached levels similar to those in group 1 patients by the ninth month of treatment (Table 7). The titre of antituberculin antibodies (according to the passive haemagglutination test) decreased gradually, the reduction being most marked in the patients in group 1. Long-term clinical and immunological results To evaluate the long-term results of treatment, the patients were divided into 3 groups. All patients suffered from similar forms of destructive pulmonary tuberculosis, were hospitalized during the same period, and were prescribed one of the above-men- tioned chemotherapy regimens. The first group (group A, controls) was composed of 61 patients who reacted favourably to the treat- ment, with complete clearance of symptoms after the main therapeutical course in the clinic. The second group (group B) consisted of 18 patients who developed a relapse of the tuberculosis process during the treatment, as manifested by extension of the cavities, revival of the perifocal inflammation, and reappearance, even for a short period, of sputum positivity. During the subsequent treatment, the cavities closed in 14 patients from this group and persisted in 4 patients. The third group (group C) was composed of 8 patients who displayed complete closure of the cavities after the completion of the chemotherapy conducted at the clinic but who developed recurrence of disease less than 2 years later. In 5 of the 8 patients the relapse was manifested by infiltrations around the residual foci; open cavities were registered in 3 patients; I patient became sputum-positive. A retrospective study of the immunological test results showed that, at admission, patients in this group already displayed a reduced number of E-rosette Table 7. Results of the specific immunological tests' according to the extent of the initial infiltrative lesions Group 1 Group 3 Test Before Before treatment 3 months 9 months treatment 3 months 9 months Blast transformation with PPD (%) 3.82 + 0.25" 8.08 ± 0.43" 4.21 ± 0.83 2.47 ± 0.14 2.97 ± 0.29 4.1 ± 0.55 Leukocyte migration inhibition with PPD 0.88 + 0.02" 0.90 + 0.03" 0.99 ± 0.05 0.42 ± 0.02 0.68 ± 0.02 0.91 ± 0.05 Passive haemagglutination with PPD (1092 titre) 6.1 ±0.32" 5.4 0.28" 3.1 ±0.29" 7.1 ± 0.24 7.3 ± 0.22 4.6 ± 0.26 ' Mean ± standard deviation. bSignificantly different from corresponding result for group 3 (P < 0.05). 767 A. G. KHOMENKO ET AL. forming lymphocytes (33.5 ± 3.35% compared with 46.2 ± 1.7% in group A, P < 0.05) and a lower level in the lymphocyte-blast transformation test with PHA (54.1 ± 2.85% compared with 70.8 ± 1.0% in group A, P < 0.05). The level of B cells (EAC-rosette forming) and the level of immunoglobulins (IgG, IgA, and IgM) did not differ significantly in the 3 groups, though it was possible to observe a slightly higher level of EAC-rosette forming lymphocytes in group B, along with a reduced IgA level (compared with normal figures). During the subsequent stages of treatment (es- pecially within the first 6 months, i.e., during the time when the patients in group B were suffering from disease recurrence), the number of E-rosette forming cells remained low in the patients in group B (39.3 ± 4.2% after 6 months of treatment), while in the patients in group A the corresponding values were within the usual limits for healthy individuals (59.1 ± 4.3%; P < 0.05 in comparison with group B). A similar pattern was observed in relation to the results of the lymphocyte-blast transformation test with PHA during the first 6 months of treatment (61.0 ± 3.42% in the patients in group B, and 78.7 ± 2.75% for group A, P < 0.05). Only at the end of the 2-year period were normal values seen in the patients from group B. The initial level of the blast transformation reac- tion with PPD (Table 8) was lower, on average, in the patients in group B. In the course of the treatment and during the follow-up period, the level remained low for a long time and increased slowly; it did not show a maximum, as seen in the patients in group A. The levels found in the specific leukocyte migration inhibition reaction increased more rapidly in the patients in group A. The level of antituberculin anti- bodies also decreased more rapidly in this group while the antibody titres in the patients from group B remained close to the initial level during several months of treatment. The results of the immunological tests in the patients from group C (patients with a delayed relapse) showed a lower number of E-rosette forming cells and a reduced lymphocyte reaction with PHA, compared with group A, at all stages of the investi- gation (Table 9). The patients in group C generally had higher levels of EAC-rosette forming lympho- cytes. The levels of IgG, IgA, and IgM in the two groups were not significantly different. The specific tests gave similar results during the initial stages of the investigation; however, after 18-24 months of treatment, we observed slightly increased levels of specific antibody and lower levels in the leukocyte migration inhibition test with PPD, in the patients from group C. DISCUSSION The tuberculosis process in newly-diagnosed patients followed diverse courses with chemotherapy: some patients displayed a rapid discontinuation of bacterial excretion and closure of the cavities. How- ever, for the majority of the patients, the healing process was much more gradual. Complete resolution of symptoms (discontinuation of bacterial excretion and closure of cavities) generally occurred after 6-9 months of treatment. The cavitation persisted in a small number of patients, and in a few cases, both sputum positivity and open cavities were still observed after 9 months of chemotherapy. At all stages of treatment, disappearance of symptoms was associated with changes in immunological parameters i.e., with a high level of specific blast transformation, with a reduced level of leukocyte migration inhibition with PPD, and with a lower level of antituberculin antibodies in the serum. The time taken for the sputum to become bac- terially negative depended on the initial intensity of excretion, with discontinuation occurring earlier in the patients with a mild initial bacterial load; the closure of cavities also occurred earlier in these patients. Similarly, the time needed for the resolution of the infiltrations depended on the initial extent of the lesions. The values found in the specific cellular tests before treatment were generally lower in the cases with heavy bacterial excretion; these values increased slowly during the treatment period. In the patients who were excreting low levels of M. tuberculosis, there was a marked and rapid increase in these immunological parameters coinciding with the time of discontinu- ation of bacterial excretion and the closure of the cavities. Similarly, patients with pronounced infiltrative lesions had low results in the E-rosette formation and lymphocyte-blast transformation tests with PHA and PPD, high values for the EAC-rosette formation test, and a strong reaction in the leukocyte migration inhibition test with PPD. Follow-up of these patients showed a delay in both the intensification of the specific blast transformation reaction and the in- crease of the values found in the migration inhibition reaction, associated with the delay in the resolution of the infiltrative lesions. A comparison of the immunological data with the clinical findings suggested that the level of the specific blast transformation and the values of the leukocyte migration inhibition reaction with PPD reflected, to a considerable degree, changes in the tuberculosis lesions. It was found that high values in these two tests were associated with more rapid closure of the cavities 768 IMMUNOLOGICAL CHARACTERISTICS OF TUBERCULOSIS PATIENTS .C 0 CO V 0 co 4-; 0 C 0 0 a 0 .C 40 LOo (0 6~~~~~~ ov B 0 Q C ,0 . _ V 00= C 0 C C 0 V 0 ~~~~~0 0 ~~~~~~~~~~~C)C~~~~~~~~~~~~~C 0 E 0* 0 *_ o E o4 ) 0 0 -- C co C ED 04' 0~~~~ 769 0c -H r-H CD CD -H 0) 0)co (N 0) Lo 0 -H -0 CD? CD 0o. 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In view of this, it appears that a strong reaction in the specific blast transformation test and a weak reaction in the leukocyte migration inhibition test reflect a high level of resistance to tuberculosis, and probably indicate the likely course of the disease. In addition, suppression of the specific blast trans- formation reaction, increase in the specific leukocyte migration inhibition, and reduction of the quantita- tive and qualitative functions of the T lymphocytes accompanied by some activation of the humoral immunity appear to be correlated with the severity and extent of infiltrative lesions. In cases with extensive lesions, the time required for resolution of the infiltration depended on the initial state of the cellular immunity, especially the specific immunity; the resolution was more rapid in patients with stable levels of T lymphocytes and high levels of blast trans- formation and migration inhibition. In the patients who developed a reactivation of the disease during the main chemotherapy course, the number of E-rosette forming lymphocytes and the values of the lymphocyte-blast transformation reaction with PHA were lower than those in the control group. These values and the results of the specific immunity tests took 18-24 months to return to normal levels. Reactivation of the disease process two years after the completion of the inpatient treatment was accom- panied by a failure in the T-lymphocyte system, which was present throughout the observation period. In some cases, patients with a reactivation of the disease also displayed suppressed specific cell-mediated immunological reactions or accelerated specific humoral immune reactions. Therefore, it seems that a strong depression of the T-lymphocyte system may be an important factor contributing to the development of reactivation of the tuberculosis process. The data obtained in this study lead us to recom- mend that immunological tests be applied during the investigation and examination of tuberculosis patients. These tests can considerably broaden our understanding of the condition of the patient, and of the status of the specific immunity of the patient. The tests have an important prognostic value, both for the rate of involution of the tuberculosis process and for the probable efficacy of the treatment. ACKNOWLEDGEMENTS Financial support for this project was received from the World Health Organization. RESUME EFFETS DE LA CHIMIOTHERAPIE SUR LES CARACTERISTIQUES IMMUNOLOGIQUES DE PATIENTS ATTEINTS DE TUBERCULOSE PULMONAIRE PRIMAIRE PROGRESSIVE Une etude immunologique a et effectuee sur 142 cas recemment diagnostiques de tuberculose pulmonaire pro- gressive. Des epreuves ont et pratiquees au moment de l'admission des patients puis a divers intervalles au cours des neuf mois de traitement en vue d'etudier les rapports entre l'etat immunologique du malade et la dimension des lesions d'infiltration et le taux d'excretion du bacille. Lors de l'admission, on a constate chez de nombreux malades des valeurs anormalement basses dans les epreuves specifiques d'immunite a mediation cellulaire (transforma- tion lymphoblastique et inhibition de la migration des leu- cocytes), ainsi que dans l'epreuve de formation de rosettes E et dans celle de transformation lymphoblastique induite par la phytohemagglutinine. En revanche, l'immunite humorale specifique (taux d'anticorps seriques diriges contre la tuberculine) etait legerement renforcee, de meme que la formation de rosettes EAC. On a montre qu'il existait une correlation positive entre la diminution des valeurs obtenues dans les epreuves d'im- munite a mediation cellulaire et, d'une part, l'etendue des lesions d'infiltration et, d'autre part, le taux d'excretion du bacille. Chez les patients presentant des infiltrations de dimension moyenne et une excretion bacillaire moderee, ces memes valeurs se sont remises a augmenter de facon plus rapide et plus importante, correlee avec la duree de negativation bacillaire et de regression des cavernes. Les epreuves d'immunite cellulaire specifique ont donne des resultats considerablement plus eleves dans le cas des patients chez qui la maladie regressait rapidement. En cas de deficit prononce de l'immunite A mediation cellulaire en general et de l'immunite specifique (anti- tuberculeuse) en particulier, on a observe une regression moins rapide des symptomes et parfois la reactivation de la maladie; ces deficits etaient toujours presents chez les patients qui ont rechute deux ans apres la fin de la phase principale de la chimiotherapie. 770 IMMUNOLOGICAL CHARACTERISTICS OF TUBERCULOSIS PATIENTS 771 REFERENCES 1. AVERBACH, M. M. [Immunology and immuno- pathology of tuberculosis.] Moscow, Medicina, 1976, pp. 177-217 (in Russian). 2. KHOMENKO, A. G. ET AL. Probleme de tuberculoza, (4): 13-17 (1979). 3. SHIMA, K. ET AL. Kekkaku, 51: 363-368 (1976). 4. BHATNAGAR, R. & MALAVIJA, A. American review of respiratory diseases, 115: 207-212 (1977). 5. GERGERT, V. J. ET AL. Probleme de tuberculoza, (8): 17-21 (1976). 6. CERNUSENKO, E. F. & KOGOSOVA, L. S. [Immuno- logical investigations in the course of treatment.] Kiev, Zdorovja, 1978 (in Russian). 7. LING, N. R. Lymphocyte stimulation, Amsterdam, North Holland Publishing Company, 1968. 8. JONDAL, M. ET AL. Journal of experimental medicine, 136: 207-215 (1972). 9. MENDES, N. F. ET AL. Journal of immunology, 111: 860-867 (1973). 10. MANCINI, G. ET AL. Immunochemistry, 2: 235-256 (1965). 11. GORINA, L. G. & OLOVNIKOV, A. M. Laboratornoe delo, (4): 247-250 (1975).