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

Abstract

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 γ-herpesvirus (γHV68) in Ig-/- μMT 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 γHV68 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 γHV68 nor the minimally persistent M3LacZ primes the T cell response to the extent that a WT γHV68 challenge fails to establish latency in the μMT mice. Memory CD4+ and CD8+ T cells thus act together to limit γHV68 infection but are unable to provide absolute protection against a high-dose, homologous challenge.