Intraepithelial lymphocytes (IEL) are a critical effector component of the gut-associated lymphoid tissue (GALT) and play an important role in mucosal immunity as well as in the maintenance of the epithelial cell integrity and barrier function. The objective of this study was to determine whether simian immunodeficiency virus (SIV)
infection of rhesus macaques would cause alterations in the immunophenotypic profiles of IEL and their
mitogen-specific
cytokine (
gamma interferon [IFN-gamma] and
MIP-1beta) responses (by flow cytometry) and virus-specific cytotoxic T-cell (CTL) activity (by the
chromium release assay). Virally infected IEL were detected through the entire course of SIV
infection by in situ hybridization. Severe depletion of CD4(+) single-positive and CD4(+)CD8(+) double-positive T cells occurred early in primary SIV
infection, which was coincident with an increased prevalence of CD8(+) T cells. This was in contrast to a gradual depletion of CD4(+) T cells in peripheral blood. The CD8(+) IEL were the primary producers of IFN-gamma and
MIP-1beta and were found to retain their potential to produce both IFN-gamma and
MIP-1beta through the entire course of SIV
infection. SIV-specific CTL activity was detected in primary IEL at 1, 2, and 4 weeks post-SIV
infection. These results demonstrated that IEL may be involved in generating
antiviral immune responses early in SIV
infection and in suppressing
viral infection thereafter. Alterations in homeostasis in epithelia due to severe CD4(+) T-cell depletion accompanied by changes in the
cytokine and
chemokine production by IEL may play a role in the enteropathogenesis of SIV
infection.