Ig heavy chain complex-linked genes influence the immune response in a murine cryptococcal infection

A murine pulmonary infection with Cryptococcus neoformans (Cne) has been us ed to determine mechanisms regulating effective T cell-mediated immunity in the lungs. In BALB/c and C.B-17 mice, following intratracheal deposition o f Cne, the fungus initially grows rapidly and is then progressively cleared from the lungs. Cne clearance in C.B-17 mice requires CD4 and CD8 T cells, IFN-gamma, and NO. Clearance in congenic BALB/c mice proceeds more slowly than in C.B-17 mice, even though the only genetic difference between these strains is at the Ig H chain-containing region of chromosome 12, Examinatio n of the pulmonary immune response in the two strains revealed that both cl eared lung Cne by T cell-dependent mechanisms and generated equivalent leve ls of NO. Furthermore, both strains recruited equal numbers of macrophages, lymphocytes, and neutrophils to the lungs, although BALB/c mice recruited higher numbers of eosinophils, Notably, leukocytes isolated from BALB/c lun gs during infection secreted lower levels of IFN-gamma and higher levels of the Th2 cytokines IL-4 and IL-5 as compared with lung leukocytes from C.B- 17 mice. Furthermore, serum levels of IgM, IgG1, IgG2a, and IgG3 anti-Cne A bs generated during infection were significantly greater in BALB/c mice tha n C.B-17 mice. These data suggest that although both BALB/c and C.B-17 mice clear pulmonary cryptococcosis through T cell-mediated mechanisms, Ig H ch ain-linked genes in BALB/c mice are associated with a decreased effectivene ss of the host response, which we suggest might influence the balance in Th 1/Th2 T cell subset development or increase anti-Cne Abs, or both.