Distinct CD8 T Cell Functions Mediate Susceptibility to Histoplasmosis During Chronic Viral Infection

• Published in: The Journal of immunology (1950) Vol. 167; no. 8; pp. 4566 - 4573
• Main Authors: Wu-Hsieh, Betty A, Whitmire, Jason K, de Fries, Rici, Lin, Jr-Shiuan, Matloubian, Mehrdad, Ahmed, Rafi
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.10.2001
• Subjects: Animals; Arenaviridae Infections - complications; Arenaviridae Infections - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chronic Disease; Disease Susceptibility; Histoplasma; Histoplasmosis - complications; Histoplasmosis - immunology; Immune Tolerance; Lymphocyte Depletion; Lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Lymphoid Tissue - immunology; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - immunology; Mice; Perforin; Pore Forming Cytotoxic Proteins; Spleen - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.8.4566

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.