Abstract
Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary lymphatic compartments, has been suggested as a mechanism of HIV/simian immunodeficiency virus (SIV)-pathogenesis. However, the role of immune activation of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In this study, we compared the expression of immune activation markers (CD69 and HLA-DR) on CD8+ T cells in the peripheral blood and lymph nodes (LNs) of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA-DR+ T cells in all these anatomical compartments than uninfected macaques. LNs that located close to the gastrointestinal (GI) tract (colon, mesenteric, and iliac LNs) of SIV-infected macaques had profoundly lower numbers of CD4+ T cells, but no significant difference in expression of activation marker (CD8+CD69+ and CD8+HLA-DR+) as compared with the peripheral lymphatic tissues (axillary and inguinal LNs). The CD4/CD8 ratios were negatively correlated with the activation of CD8+ T cells in the overall LNs, with further associations with CD8+HLA-DR+ in GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the increase of CD8+ T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.
Highlights
Persistent immune activation is a hallmark of HIV infection in humans and simian immunodeficiency virus (SIV) infection in the non-natural host rhesus macaques [1,2,3]
We found that SIV infection significantly reduced the proportion of CD4+ T cells and CD4/CD8 ratios in both the peripheral blood and lymph nodes (LNs)
The most severe impairment of T-cell homeostasis occurs at the intestinal mucosa, as evidenced by a severe depletion of CD4+ T cells in the intraepithelial lymphocytes (IELs) isolated from colon and jejunum
Summary
Persistent immune activation is a hallmark of HIV infection in humans and simian immunodeficiency virus (SIV) infection in the non-natural host rhesus macaques [1,2,3]. Microbial translocation at the gastrointestinal (GI) tract represents a major stimulus for immune activation that persists even after control of HIV replication [4, 5]. There is an extensive depletion of CD4+ T memory cells in gut lymphoid tissues within 4–6 weeks of HIV infection [10]. This immune dysregulation at the GALT mucosa is implicated in HIV enteropathy, accounting for approximately 60–80% of diarrhea in HIV-infected patients sometime during their illness, representing the most common clinical manifestation of AIDS [11]
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