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Andreansky, S.* ; Liu, H.* ; Adler, H. ; Koszinowski, U.H.* ; Efstathiou, S.* ; Doherty, P.C.*

The limits of protection by "memory" T cells in lg -/-mice persistently infected with a γ-herpesvirus.

Proc. Natl. Acad. Sci. U.S.A. 101, 2017-2022 (2004)

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Can CD4(+) and CD8(+) "memory" T cells that are generated and maintained in the context of low-level virus persistence protect, in the absence of antibody, against a repeat challenge with the same pathogen? Although immune T cells exert effective, long-term control of a persistent gamma-herpesvirus (gammaHV68) in Ig(-/-) microMT mice, subsequent exposure to a high dose of the same virus leads to further low-level replication in the lung. This lytic phase in the respiratory tract is dealt with effectively by the recall of memory T cells induced by a gammaHV68 recombinant (M3LacZ) that does not express the viral M3 chemokine binding protein. At least for the CD8(+) response, greater numbers of memory T cells confer enhanced protection in the M3LacZ-immune mice. However, neither WT gammaHV68 nor the minimally persistent M3LacZ primes the T cell response to the extent that a WT gammaHV68 challenge fails to establish latency in the microMT mice. Memory CD4(+) and CD8(+) T cells thus act together to limit gammaHV68 infection but are unable to provide absolute protection against a high-dose, homologous challenge.

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