title: Distinct CD8 T cell functions mediate susceptibility to histoplasmosis during chronic viral infection.
abstract: It has long been recognized that some viral infections result in generalized immune suppression. In acute infections, this period of suppressed immunity is relatively short. However, chronic infections associated with a prolonged period of immune suppression present far greater risks. Here, we examined the role of CD8 T cell responses following viral infection in immunity to systemic histoplasmosis. Although wild-type mice with systemic histoplasmosis were able to control the infection, those simultaneously infected with lymphocytic choriomeningitis virus clone 13 showed reduced immunity with greater fungal burden and high mortality. The immune suppression was associated with loss of CD4 T cells and B cells, generalized splenic atrophy, and inability to mount a granulomatous response. Removing the anti-viral CD8 T cells in the coinfected mice enabled them to reduce the fungal burden and survive the infection. Their lymphoid organs were replenished with CD4 T and B cells. In contrast to wild-type mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus clone 13 and Histoplasma showed an absence of immunopathology, but the animals still died. These results show that CD8 T cells can suppress immunity through different mechanisms; although immunopathology is perforin-dependent, lethality is perforin-independent.
authors.affiliation: Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan. wuhsiehb@ha.mc.ntu.edu.tw
authors.forename: B A
authors.initials: BA
authors.lastname: Wu-Hsieh
authors.forename: J K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: R
authors.initials: R
authors.lastname: de Fries
authors.forename: J S
authors.initials: JS
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Matloubian
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000150:complications / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D004198:Disease Susceptibility; D006660:Histoplasmosis / Q000150:complications / Q000276:immunology*; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013154:Spleen / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin