Mechanisms associated with immunoregulation in human American cutaneous leishmaniasis

Mechanisms possibly involved in the regulation of the immune response were evaluated in 49 patients with American cutaneous leishmaniasis (ACL). The patients were classified on the basis of clinical and histopathological criteria as suffering localized (LCL), mucocutaneous (MCL) or diffuse (DCL) forms of the disease. A significant leishmanial antigen-induced suppression of in vitro mitogen responsiveness was demonstrated in the DCL group, but not in the other two diseases states. Lack of suppressive activity was particularly evident in MCL, this being the group that presented the highest in vivo and in vitro reactivity to the parasite antigens. In fact, a significant inverse correlation was found between the degree of suppression and the antigen-induced lymphocyte proliferative response. In contrast, a mixture of mononuclear cells from MCL patients and normal subjects showed higher that expected responses to mitogen, while this increase was not observed in co-cultures of DCL and normal mononuclear cells. Due to their possible modulatory influences, circulating immune complexes were also evaluated in these patient groups, higher levels being found in MCL and DCL patients than in either LCL or controls. The possible mechanisms involved in the regulation of the immune response to the protozoan in the complex disease spectrum of ACL are discussed in relation to anergy in DCL and hyperresponsiveness in MCL.