CHANGES IN CELLULAR-RESPONSE TO MYCOBACTERIAL ANTIGENS AND CYTOKINE PRODUCTION PATTERNS IN LEPROSY PATIENTS DURING MULTIPLE-DRUG THERAPY

Changes in Mycobacterium leprae-induced lymphoproliferative responses and mediator release by leprosy patients' lymphocytes were followed du ring multiple drug therapy (MDT). At the time of diagnosis, multibacil lary (MB) patients who did not develop reactions responded to both son icated M. leprae and synthetic disaccharide coupled to bovine serum al bumin (ND-BSA) antigens, but those who would later develop reactions d id not respond, even in the presence of added cytokines. The paucibaci llary (PB) group initially had high responses to sonicated M. leprae b ut no response to ND-BSA, even in the presence of added cytokines. In the first year of treatment, the supernatants of PB patients' cell cul tures contained factors that enhanced the phytohaemagglutinin (PHA) re sponse of normal cells. In contrast, those MB patients who did not dev elop reactions at a later stage produced culture supernatants that wer e inhibitory. Interestingly, the MB patients who later developed react ions during treatment, and did not initially respond to M. leprae, pro duced supernatants containing enhancing factors, like those of the PB group. Later on in the treatment, all patients had the same patterns: when response to M. leprae decreased from its highest level, inhibitor y factors were produced. Further studies revealed that the supernatant s which inhibited the PHA response of normal cells contained the activ e form of transforming growth factor-beta(1) (TGF-beta(1)), whatever t he disease type or treatment status of the donor. These TGF-beta(1) le vels correlated directly with the degree of inhibition. Similarly, sup ernatants that neither inhibited nor enhanced PHA responses contained the highest levels of interleukin-10 (IL-10), while those from treated patients that enhanced contained the lowest levels of interleukin-4 ( IL-4) and interferon-gamma (IFN-gamma). These cytokine correlations tr anscended the conventional disease classification, and imply that all patients pass through a sequence of patterns of immune response during treatment. These treatment-induced changes may explain occasional rep orts of response patterns at variance with the 'immunological spectrum ' of leprosy.