T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy

Abstract

In some subjects the infective agent of leprosy, Mycobacterium leprae, causes disseminated (lepromatous) disease. Such subjects have a major role in the transmission of the disease and show deficient T-cell responses both in vivo and in vitro to M. leprae, but not to other antigens. Numerous studies have recently shown that T cells with functional capabilities after initial triggering with antigen can be maintained in a state of continuous proliferation in vitro when cultured in medium containing interleukin 2 (IL-2). Here we have studied the effect of IL-2 rich T-cell conditioned medium on lepromatous peripheral blood mononuclear cells. Our results show that although lepromatous T cells fail to produce IL-2 after exposure to M. leprae they can respond by proliferation to M. leprae in the presence of T-cell conditioned medium, suggesting that the unresponsiveness in lepromatous leprosy results from a deficiency in the production of IL-2 or related factors and not a lack of M. leprae-reactive T cells.

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

“…These facts suggest that the absence of IL-2 production per se is not responsible for the anergic state. Our results conflict with the reports that responsiveness is restored after exposure of the cells to exogenous IL-2 (10,28). The discrepancy between our results and those of Haregewoin et al (10) might be attributed to the heterogeneity of responsiveness of the lepromatous patients.…”

“…Our results conflict with the reports that responsiveness is restored after exposure of the cells to exogenous IL-2 (10,28). The discrepancy between our results and those of Haregewoin et al (10) might be attributed to the heterogeneity of responsiveness of the lepromatous patients. Attempts to restore responsiveness with exogenous IL-2 would appear to be successful if many of the patients tested are low responders rather than nonresponders.…”

“…Studies from our laboratory (8) and those of others (10,27,28) have attempted to elucidate the capacity of IL-2 to reverse the unresponsiveness of T cells from patients with iepromatous leprosy. In the present study this parameter has been studied with an appreciation of the variable responses of lepromatous leprosy patients to M. leprae.…”

“…The exposure of peripheral blood T cells to M. leprae fails to result in appreciable T cell proliferation and synthesis of lymphokine, including IFN-3" (8-10). In contrast, the lymphocytes of patients with lepromatous leprosy can respond to l~ctins and other antigens to which they are sensitized (4,(8)(9)(10)(11)(12)(13). This had lead to the concept of selective anergy in which, either due to the absence ofM.…”

Ruminant Paratuberculosis—a Century of Progress and Frustration

“…48 Similar immunologic defects have also been identified in leprosy and tuberculosis. 18,35,105 Although not examined in bovine paratuberculosis, the role of λδ T-cells may be important to the pathogenesis of the disease. These cells line mucosal surfaces, including intestine, and are the first line of defense in bacterial infections.…”