An early expansion of CD8αβ T cells, but depletion of resident CD8αα T cells, occurs in the intestinal epithelium during primary simian immunodeficiency virus infection

Objectives: To evaluate changes in the phenotypic heterogeneity and function of CD8 T cells in the intestinal epithelium during primary SIV infection. Design: Previous studies have shown an increased prevalence of CD8 T cells in the intestinal epithelium in HIV and SIV infections. As intestinal CD8 T cells are a heterogeneous population we evaluated their phenotypic distribution (CD8αβ, CD8αα) and function [interferon (IFN)-γ production] during primary SIV infection. Methods: The phenotype and functional potential of CD8 intestinal intraepithelial lymphocytes (IEL) prior to and following SIV infection were determined using flow cytometry. Results: IEL were found to harbor CD8αβCD3, CD8ααCD3 and CD8αα+CD3- T-cell subsets. Most of the CD8CD4 double positive IEL expressed CD8αα homodimers. In primary SIV infection the frequency of CD8αβCD3 T cells increased dramatically whereas the frequency of CD8αα T cells declined. A higher frequency of CD8αβKi-67 IEL was observed following SIV infection suggesting that local cell proliferation might have contributed to an increased prevalence of CD8αβ IEL. In contrast, a severe depletion of CD8ααCD4 IEL occurred which contributed to the depletion of CD8αα IEL. The CD8αβ IEL were the major producers of IFN-γ in the intestinal epithelium and the frequency of IFN-γ-producing CD8αβ IEL was enhanced considerably in primary infection. Conclusions: CD8αβ IEL may be important in generating early antiviral responses at the intestinal epithelium. However, alterations in CD8 T-cell subsets and their function may reflect early immunopathogenic events in the intestinal mucosa. (C) 2000 Lippincott Williams and Wilkins.