title: Ig heavy chain complex-linked genes influence the immune response in a murine cryptococcal infection.
abstract: A murine pulmonary infection with Cryptococcus neoformans (Cne) has been used to determine mechanisms regulating effective T cell-mediated immunity in the lungs. In BALB/c and C.B-17 mice, following intratracheal deposition of 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. Examination of the pulmonary immune response in the two strains revealed that both cleared lung Cne by T cell-dependent mechanisms and generated equivalent levels 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 lungs 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 Abs generated during infection were significantly greater in BALB/c mice than 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 chain-linked genes in BALB/c mice are associated with a decreased effectiveness of the host response, which we suggest might influence the balance in Th1/Th2 T cell subset development or increase anti-Cne Abs, or both.
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lovchik
authors.forename: J A
authors.initials: JA
authors.lastname: Wilder
authors.forename: G B
authors.initials: GB
authors.lastname: Huffnagle
authors.forename: R
authors.initials: R
authors.lastname: Riblet
authors.forename: C R
authors.initials: CR
authors.lastname: Lyons
authors.forename: M F
authors.initials: MF
authors.lastname: Lipscomb
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D002465:Cell Movement / Q000276:immunology; D003453:Cryptococcosis / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D008040:Genetic Linkage / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D000908:Antibodies, Fungal; D016207:Cytokines; D007143:Immunoglobulin Heavy Chains