Reversal by interleukin-2 of the T cell unresponsiveness of lepromatous leprosy to Mycobacterium leprae

Abstract

In some subjects Mycobacterium leprae causes disseminated (lepromatous) disease. Such subjects show both in vivo and in vitro deficient T cell responses to M. leprae, but not to other antigens. We have recently shown that lepromatous peripheral blood mononuclear cells (PBMC) failed to produce interleukin 2 (IL-2) in response to M. leprae and that T cell-conditioned media (TCM) can reverse the T cell unresponsiveness in a majority of lepromatous leprosy patients (Haregewoin et al. 1983). Here we show that highly purified and recombinant IL-2 had effects similar to TCM. On the other hand, lepromatous PBMC produced IL-1, and IL-1 had no restorative effect. These findings provide further evidence that the unresponsiveness in lepromatous leprosy often results from a deficiency in IL-2 production. After initial stimulation with TCM + M. leprae, lepromatous PBMC could be restimulated with M. leprae alone, providing clear evidence that M. leprae-reactive lymphocytes were generated in the presence of TCM. The present findings are discussed in relation to the possible mechanisms involved in the failure of IL-2 production. If our findings can be reproduced in vivo, IL-2 may offer a novel approach to therapy in lepromatous leprosy.