CD8(+) T cells control ross river virus infection in musculoskeletal tissues of infected mice

Autor(es): Burrack, Kristina S.; Montgomery, Stephanie A.; Homann, Dirk; Morrison, Thomas E.


Resumo: 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(-/-) A 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.


Palavras-Chave: Neurovirulent Sindbis virus; Chikungunya virus; Mouse model; Epidemic Polyarthritis; Nonhematopoietic cells; Arthritogenic disease; Alphavirus infection; Hemorrhagic -Fever; Immune - Response; Aedes aegypti


Imprenta: Journal of Immunology, v. 194, n. 2, p. 678-689, 2015


Identificador do objeto digital: 10.4049/jimmunol.1401833


Descritores: Aedes aegypti - Cell ; Aedes aegypti - Immune response ; Aedes aegypti - Molecular structure ; Aedes aegypti - Viral infections ; Aedes aegypti - Chikungunya Fever


Data de publicação: 2015