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alpha 4(+)beta 7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection

  1. Author:
    Kader, M.
    Wang, X.
    Piatak, M.
    Lifson, J.
    Roederer, M.
    Veazey, R.
    Mattapallil, J. J.

  2. Author Address

    Kader, M.; Mattapallil, J. J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Wang, X.; Veazey, R.] Tulane Natl Reg Primate Ctr, Covington, LA USA. [Piatak, M.; Lifson, J.] NCI, SAIC, Frederick, MD 21701 USA. [Roederer, M.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
    1. Year: 2009
  2. Journal: Mucosal Immunology
    1. 2
    2. 5
    3. Pages: 439-449
  4. Type of Article: Article
  1. Abstract:

    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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  2. DOI: 10.1038/mi.2009.90
  3. PMID: 19571800

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