Gastrointestinal Epithelium Is an Early Extrathymic Site for Increased Prevalence of CD34+ Progenitor Cells in Contrast to the Thymus during Primary Simian Immunodeficiency Virus Infection

The objective of this study was to determine the effects of primary simian immunodeficiency virus (SIV) infection on the prevalence and phenotype of progenitor cells present in the gastrointestinal epithelia of SIV-infected rhesus macaques, a primate model for human immunodeficiency virus pathogenesis. The gastrointestinal epithelium was residence to progenitor cells expressing CD34 antigen, a subset of which also coexpressed Thy-1 and c-kit receptors, suggesting that the CD34 1 population in the intestine comprised a subpopulation of primitive precursors. Following experimental SIVmac251 infection, an early increase in the proportions of CD34 1 Thy-1 1 and CD34 1 c-kit 1 progenitor cells was observed in the gastrointestinal epithelium. In contrast, the proportion of CD34 1 cells in the thymus declined during primary SIV infection, which was characterized by a decrease in the frequency of CD34 1 Thy-1 1 progenitor cells. A severe depletion in the frequency of CD4-committed CD34 1 progenitors was observed in the gastrointestinal epithelium 2 weeks after SIV infection which persisted even 4 weeks after infection. A coincident increase in the frequency of CD8committed CD34 1 progenitor cells was observed during primary SIV infection. These results indicate that in contrast to the primary lymphoid organs such as the thymus, the gastrointestinal epithelium may be an early extrathymic site for the increased prevalence of both primitive and committed CD34 1 progenitor cells. The gastrointestinal epithelium may potentially play an important role in maintaining T-cell homeostasis in the intestinal mucosa during primary SIV infection. Human immunodeficiency virus (HIV) infection has been demonstrated to cause a progressive loss in the frequency of hematopoietic progenitors in the bone marrow, thymus, and peripheral blood of HIV-seropositive individuals (2, 14, 15, 16, 23, 26, 29, 32, 48, 56, 57). Recent studies with the murine model have demonstrated that gastrointestinal epithelium can function as an extrathymic site for T-cell differentiation and maturation (41, 42). There is no information available, however, on the effects of HIV infection on T-cell maturation or differentiation and progenitor cell frequency in intestinal epithelium. The intestinal epithelium, like the thymic epithelium, has been shown to be capable of supporting T-cell differentiation and maturation (36) and also of carrying out negative and positive selection of T cells (42). Since gastrointestinal lymphoid tissue harbors more than 90% of the total lymphocytes in the body, a high level of T-cell turnover may occur at this site. The development and maturation of T cells from tissue progenitors that might have migrated into the gastrointestinal epithelium may be one of the mechanisms for maintaining T-cell homeostasis at these sites. Progenitor cells capable of generating mature T cells have been isolated from cryptopatches of the mouse intestinal epithelium (45). Murine intestinal epithelial cells were shown to secrete the c-kit ligand called stem cell factor (SCF), which supports T-cell differen