Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection

We investigated simian immunodeficiency virus (SIV)-specific CD4(+) T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIV Delta nef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIV Delta nef animals were predominantly CD27(-)CD28(-)CD45RA(low)CCR7(-)CCR5(-), consistent with an effector-memory subset, and included a fully differentiated CD45RA(+)CCR7(-) subpopulation. In contrast, SIV-specific CD4(+) T cells from SIV-infected animals were mostly CD27(+)C D28(+)CD45RA(-)CCR7(+)CCR5(+), consistent with an early central memory phenotype. The CD45RA(+)CCR7(-)CD(4+) subset from SIV Delta nef animals was highly enriched for effector CD4(+) T cells, as indicated by the perforin expression and up- regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4(+) T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIV Delta nef to induce a high frequency virus-specific CD4(+)T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.