Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 1, Pages 141-153Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.1.141
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Funding
- NIAID NIH HHS [R56 AI059603, R01 AI059603-03, R01 AI059603, AI 59603] Funding Source: Medline
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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 (gamma HV) 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-7 alpha, IL-2/IL-15 beta). 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 gamma HV68 splenic latency. These observations provide evidence that functional CD8(+) memory T cells can be generated and maintained during low-load gamma HV68 persistence.
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