Specific suppression of responses to Leishmania tropica by a cloned T-cell line

Abstract

Most clinical cases of cutaneous leishmaniasis caused by Leishmania tropica major consist of self-healing lesions that are associated with the development of strong specific cell-mediated immunity (CMI) detected by delayed-type hypersensitivity (DTH)^1,2. At the other extreme are susceptible individuals who develop persistent or diffuse forms of the disease. This spectrum of cutaneous leishmaniasis can be reproduced in in-bred mouse strains according to their genetic constitution³. BALB/c mice are exceptionally susceptible: the disease can be induced with minimum infecting doses and is inexorably progressive, terminating in cutaneous and fatal visceral metastasis^3–7. In this case, potentially curative CMI is abrogated by the generation of a specific Lyt-1⁺2⁻, I-J⁻ population of suppressor T (T_s) cells^8,9, whose induction is probably secondary to a primary macrophage defect^10,11 controlled by a single major non-H–2-linked autosomal gene^5,6. The generation of the T_s cells can be prevented and infection cured by prior sublethal (550 rad) irradiation⁸. The potency of the T_s cells is such that as few as 10⁶ cells transferred adoptively can completely reverse this prophylactic effect⁹. In view of their potency and potential relevance to clinical leishmaniasis, I have now studied T_s cells at the clonal level to delineate further their functional characteristics and interaction with the effector mechanism. I report here a cloned T-cell line expressing specific suppression against in vitro lymphocyte proliferation and in vivo induction of DTH to L. tropica antigens.