Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies.
On a B10 genetic background noncure and cure phenotypes for murine visceral leishmaniasis are controlled by H-2. In this report results are presented which show the effects of administering specific anti-I-A and anti-I-E monoclonal antibodies to B10.D2/n (H-2d) noncure mice prior to and during 85 days of infection with Leishmania donovani LV9. The effects of the two anti-Ia antibodies were precisely equivalent in diminishing circulating anti-leishmanial IgG levels throughout infection, possibly as a direct effect of the anti-Ia antibodies in reducing the splenic B cell population. In terms of resolution of liver and spleen parasite loads, which is known to be dependent upon induction of a cell-mediated immune response, dramatically different results were obtained with the two anti-Ia antibodies. Anti-I-A treatment resulted in prolonged exacerbation of disease in liver and spleen. Anti-I-E treatment was associated with enhanced clearance of liver and spleen parasite loads beyond 30 days of infection. The results are consistent with the hypothesis that blocking major histocompatibility complex-restricted antigen presentation by one class II molecule allows T cell responses controlled by the other to predominate. Hence, in H-2d mice, I-E controls suppressor activity while I-A is associated with helper activity for cell-mediated control of infection. The results offer some prospect for the development of haplotype- and class II molecule-specific immunotherapeutic regimens in the host which might prevent the undesirable expansion of T cell populations which exacerbate disease without compromising development of a curative cell-mediated immune response.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007893:Leishmania donovani / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000628:therapy*; D008099:Liver / Q000469:parasitology; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D013154:Spleen / Q000469:parasitology
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007074:Immunoglobulin G