Memory Generation and Maintenance of CD8+ T Cell Function during Viral Persistence1
| Autor: | Cush, Stephanie S., Anderson, Kathleen M., Ravneberg, David H., Weslow-Schmidt, Janet L., Flaño, Emilio |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Cytotoxicity
Immunologic Mice Inbred BALB C Receptors Antigen T-Cell Epitopes T-Lymphocyte Cell Differentiation Herpesviridae Infections CD8-Positive T-Lymphocytes Viral Load Article Virus Latency Mice Inbred C57BL Mice Gammaherpesvirinae NIH 3T3 Cells Animals Homeostasis Receptors Cytokine Immunologic Memory |
| Popis: | During infection with viruses that establish latency, the immune system needs to maintain lifelong control of the infectious agent in the presence of persistent Ag. By using a gamma-herpesvirus (gammaHV) infection model, we demonstrate that a small number of virus-specific central-memory CD8+ T cells develop early during infection, and that virus-specific CD8+T cells maintain functional and protective capacities during chronic infection despite low-level Ag persistence. During the primary immune response, we show generation of CD8+ memory T cell precursors expressing lymphoid homing molecules (CCR7, L-selectin) and homeostatic cytokine receptors (IL-7alpha, IL-2/IL-15beta). During long-term persistent infection, central-memory cells constitute 20-50% of the virus-specific CD8+ T cell population and maintain the expression of L-selectin, CCR7, and IL-7R molecules. Functional analyses demonstrate that during viral persistence: 1) CD8+ T cells maintain TCR affinity for peptide/MHC complexes, 2) the functional avidity of CD8+ T cells measured as the capacity to produce IFN-gamma is preserved intact, and 3) virus-specific CD8+ T cells have in vivo killing capacity. Next, we demonstrate that at 8 mo post-virus inoculation, long-term CD8+ T cells are capable of mediating a protective recall response against the establishment of gammaHV68 splenic latency. These observations provide evidence that functional CD8+ memory T cells can be generated and maintained during low-load gammaHV68 persistence. |
| Databáze: | OpenAIRE |
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