B lymphocytes are required for the generation of T cells that mediate healing of cutaneous leishmaniasis.
The role that B lymphocytes and/or antibodies play in the healing of Leishmania major infections in genetically resistant C3H/HeN mice was investigated by monitoring the course of infection in animals that had been B cell depleted by treatment from birth with anti-IgM sera (mu-suppressed). L. major infection of mu-suppressed C3H/HeN mice produced lesions that were significantly larger than those induced in control animals, and failed to heal. Moreover, vaccinated mu-suppressed mice also developed chronic nonhealing infections, although their lesions were initially smaller than those developed by nonvaccinated mu-suppressed controls. The enhanced susceptibility of mu-suppressed mice could be completely overcome by adoptive transfer of T lymphocytes from mice that had spontaneously healed their lesions, and to a lesser extent by T lymphocytes from normal animals. Anti-leishmanial antibody responses were completely absent in mu-suppressed mice, regardless of whether they were lymphocyte reconstituted, whereas delayed type hypersensitivity (DTH) to leishmanial antigens was present in normal and mu-suppressed animals. The ability of immune T cells to protect mu-suppressed mice without restoring humoral responsiveness clearly indicates that antibodies are not necessary for healing leishmanial infections. Instead, the observed effect of mu-suppression argues that B lymphocytes are required for the generation of an effector T cell population, apparently unrelated to DTH, which mediates the healing of cutaneous lesions. These results thus provide the first evidence for the B cell and/or Ig dependency of a T cell population that is critical for the development of immunity against a microbial agent.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007116:Immunization, Passive; D007075:Immunoglobulin M / Q000008:administration & dosage; D007896:Leishmaniasis / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; C044203:anti-IgM