An early expansion of CD8 alpha beta T cells, but depletion of resident CD8 alpha alpha T cells, occurs in the intestinal epithelium during primary simian immunodeficiency virus infection

Objectives: To evaluate changes in the phenotypic heterogeneity and functio n 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 distrib ution (CD8 alpha beta, CD8 alpha alpha) and function [interferon (IFN)-gamm a production] during primary SIV infection. Methods: The phenotype and functional potential of CD8 intestinal intraepit helial lymphocytes (IEL) prior to and following SIV infection were determin ed using flow cytometry. Results: IEL were found to harbor CD8 alpha beta CD3, CD8 alpha alpha CD3 a nd CD8 alpha alpha+CD3- T-cell subsets. Most of the CD8CD4 double positive IEL expressed CD8 alpha alpha homodimers. In primary SIV infection the freq uency of CD8 alpha beta CD3 T cells increased dramatically whereas the freq uency of CD8 alpha alpha T cells declined. A higher frequency of CD8 alpha beta Ki-67 IEL was observed following SIV infection suggesting that local c ell proliferation might have contributed to an increased prevalence of CD8 alpha beta IEL. In contrast, a severe depletion of CD8 alpha alpha CD4 IEL occurred which contributed to the depletion of CD8 alpha alpha IEL. The CD8 alpha beta IEL were the major producers of IFN-gamma in the intestinal epi thelium and the frequency of IFN-gamma-producing CD8 alpha beta IEL was enh anced considerably in primary infection. Conclusions: CD8 alpha beta IEL may be important in generating early antivi ral responses at the intestinal epithelium. However, alterations in CD8 T-c ell subsets and their function may reflect early immunopathogenic events in the intestinal mucosa. (C) 2000 Lippincott Williams & Wilkins.