Modulation of Cell-Mediated Immunity in Experimental Cutaneous Leishmaniasis

Abstract

It is now generally accepted that cell-mediated immunity plays a causal role in acquired resistance to leishmaniasis. This is based on an impressive range of clinical and experimental evidence (Table 1). Patients with active visceral leishmaniasis failed to respond to L. donovani antigens in delayed-type hypersensitivity (DTH) skin test (Rezai et al, 1978) and in lymphocyte proliferation assay in vitro (Ho et al, 1983). The patients developed a positive skin test and resistance to challenge with L. donovani following successful antimony therapy (Carvalho et al, 1981). Resistant strains of mice rendered relatively T cell deficient by adult thymectomy followed by irradiation and reconstitution with syngeneic bone marrow cells are less able to control L. major infection and have delayed healing (Preston et al, 1972). Athymic mutants of the highly resistant CBA and C57BL/6 mice are totally unable to control L. major infection which progresses and visceralises. Normal resistance can be fully restored by reconstituting these T cell deficient mutants with syngeneic T cells (Mitchell et al, 1980). Acquired protective immunity to L. major (Preston and Dumonde, 1976) and L. donovani (Rezai, Farrell and Soulsby, 1980) in resistant or susceptible mice ban be adoptively transferred by T cells but not by B cells (Liew, Hale and Howard, 1982; Liew, Howard and Hale, 1984). Treatment of resistant C3H mice from birth with anti-IgM antibody rendered them defective in antibody response and also susceptible to L. major infection. However, lesion progression in these treated mice can be arrested and the disease outcome reversed by adoptive transfer of T cell alone from normal C3H donors (Scott, Natovitz and Sher, 1986) without any restoration of humoral antibody formation.