Regulation of cell-mediated immunity in cutaneous leishmaniasis.

Abstract

There is now good evidence that cell-mediated immunity (CMI) rather than humoral antibody plays a causal role in acquired immunity to leishmaniasis. In genetically susceptible strains of mice, the failure to control the disease progression is associated with a population of Lyt-2-T cells which can prevent the induction or expression of curative CMI and hence exacerbate disease development. Susceptible BALB/c mice can be rendered resistant to L. major infection by prior sublethal dose gamma-irradiation, anti-mu antibody treatment from birth, anti-L3T4 antibody treatment or intravenous (i.v.) or intraperitoneal (i.p.) route of immunisation with killed L. major promastigotes or isolated leishmanial antigens. The route of immunisation, however, appears crucial in the induction of prophylactic immunity. Subcutaneous (s.c.) and intramuscular routes of immunisation with killed promastigotes are not only ineffective, they induce a population of Lyt-2- L3T4+ T cells which inhibit the prophylactic effect of i.v. immunisation. Although both the disease-promoting T cells and the host-protective T cells express the same phenotypic cell surface markers, they differ functionally. Protective T cells produce interferon-gamma (IFN-gamma) and macrophage-activating factor (MAF) when cultured in vitro with leishmanial antigens, whereas the disease-promoting T cells do not. In addition, these latter cells are able to produce substances in their antigen-specific culture supernatant which inhibits the MAF activity of the host protective T cells.(ABSTRACT TRUNCATED AT 250 WORDS)