Journal
MUCOSAL IMMUNOLOGY
Volume 2, Issue 5, Pages 439-449Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2009.90
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Funding
- National Institutes of Allergy and Infectious diseases (NIAID) [K22AI07812]
- National Institute of Dental and Craniofacial Research (NIDCR) [R21DE018339]
- National Cancer Institute
- National Institutes of Health [N01-CO-12400, HHSN266200400088C]
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Human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infections are believed to infect minimally activated CD4(+) T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4(+) T cells that express high levels of the alpha 4 beta 7 heterodimer are preferentially infected very early during the course of SIV infection. At days 2-4 post infection, alpha 4(+)beta 7(hi)CD4(+) T cells had similar to 5x more SIV-gag DNA than beta 7-CD4(+) T cells. alpha 4(+)beta 7(hi)CD4(+) T cells displayed a predominantly central memory (CD45RA(-)CD28(+)CCR7(+)) and a resting (CD25(-)CD69(-)HLA-DR(-)Ki67(-)) phenotype. Although the expression of detectable CCR5 was variable on alpha 4(+)beta 7(hi) and beta 7-CD4(+) T cells, both CCR5(+) and CCR5(-) subsets of alpha 4(+)beta 7(hi) and beta 7(-)CD4(+) T cells were found to express sufficient levels of CCR5 mRNA, suggesting that both these subsets could be efficiently infected by SIV. In line with this, we found similar levels of SIV infection in beta 7(-)CD4(+)CCR5(+) and beta 7(-)CD4(+)CCR5(-) T cells. alpha 4 beta 7(hi)CD4(+) T cells were found to harbor most T helper (Th)-17 cells that were significantly depleted during acute SIV infection. Taken together, our results show that resting memory alpha 4+beta 7(hi)CD4(+) T cells in the blood are preferentially infected and depleted during acute SIV infection, and the loss of these cells alters the balance between Th-17 and Th-1 responses, thereby contributing to disease pathogenesis.
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