Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti‐Ia antibodies: differential effects of anti‐I‐A vs. anti‐I‐E antibodies

Abstract

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‐2^d) 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‐2^d 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 compromizing development of a curative cell‐mediated immune response.