Leishmania donovani infection in heterozygous and recombinant H-2 haplotype mice

Abstract

On a B10 (Lsh ^s) genetic background the development of acquired T-cell-mediated immunity to Leishmania donovani infection in mice is under H-2-linked genetic control. Three phenotypic patterns of recovery were previously observed: “early cure” (H-2 ^s, H-2 ^r), “cure” (H-2 ^b) and “noncure” (H-2 ^d, H-2 ^q, H-2 ^f), with cure behaving as a recessive trait in H-2 ^b/H-2 ^d mice. In this study the long-term response to L. donovani is followed over 130 days of infection in eight recombinant haplotype strains and in six further heterozygous haplotype combinations. Noncure in B10.HTG mice, which carry d alleles for loci at the K end and b alleles for loci at the D end of H-2, confirms that H-2-linked genetic control of the acquired response to L. donovani infection is located in the K end. The complex pattern of dominance relationships observed in the additional heterozygous haplotypes studied, the variable phenotypic response of H-2 ^k mice and of recombinant haplotype strains carrying IE^k in common, and the differential early curing activity observed in heterozygotes involving the s but not the r early cure haplotype and in recombinant haplotype mice carrying s alleles to the left of IE suggest, however, that more than one subregion (IE and presumably IA) are involved. Results are interpreted in the light of immunoregulatory T-cell populations previously demonstrated in noncure, cure, and early cure strains.