title: CD8+ T cells control Ross River virus infection in musculoskeletal tissues of infected mice.
abstract: Ross River virus (RRV), chikungunya virus, and related alphaviruses cause debilitating polyarthralgia and myalgia. Mouse models of RRV and chikungunya virus have demonstrated a role for the adaptive immune response in the control of these infections. However, questions remain regarding the role for T cells in viral control, including the magnitude, location, and dynamics of CD8(+) T cell responses. To address these questions, we generated a recombinant RRV expressing the H-2(b)-restricted glycoprotein 33 (gp33) determinant derived from the glycoprotein of lymphocytic choriomeningitis virus. Using tetramers, we tracked gp33-specific CD8(+) T cells during RRV-lymphocytic choriomeningitis virus infection. We found that acute RRV infection induces activation of CD8(+) T cell responses in lymphoid and musculoskeletal tissues that peak from 10-14 d postinoculation, suggesting that CD8(+) T cells contribute to control of acute RRV infection. Mice genetically deficient for CD8(+) T cells or wild-type mice depleted of CD8(+) T cells had elevated RRV loads in skeletal muscle tissue, but not joint-associated tissues, at 14 d postinoculation, suggesting that the ability of CD8(+) T cells to control RRV infection is tissue dependent. Finally, adoptively transferred T cells were capable of reducing RRV loads in skeletal muscle tissue of Rag1(-/-) mice, indicating that T cells can contribute to the control of RRV infection in the absence of B cells and Ab. Collectively, these data demonstrate a role for T cells in the control of RRV infection and suggest that the antiviral capacity of T cells is controlled in a tissue-specific manner.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045;
authors.forename: Kristina S
authors.initials: KS
authors.lastname: Burrack
authors.affiliation: Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Montgomery
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045; Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045; Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors.forename: Dirk
authors.initials: D
authors.lastname: Homann
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045; thomas.morrison@ucdenver.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Morrison
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D064532:Histocompatibility Antigen H-2D / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012398:Ross River virus / Q000276:immunology*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D064532:Histocompatibility Antigen H-2D; D018398:Homeodomain Proteins; D014764:Viral Proteins; C064658:RAG-1 protein