title: Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection.
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 alpha4beta7 heterodimer are preferentially infected very early during the course of SIV infection. At days 2-4 post infection, alpha4(+)beta7(hi)CD4(+) T cells had approximately 5x more SIV-gag DNA than beta7(-)CD4(+) T cells. alpha4(+)beta7(hi)CD4(+) T cells displayed a predominantly central memory (CD45RA(-)CD28(+)CCR7(+)) and a resting (CD25(-)CD69(-)HLA-DR(-)Ki-67(-)) phenotype. Although the expression of detectable CCR5 was variable on alpha4(+)beta7(hi) and beta7(-)CD4(+) T cells, both CCR5(+) and CCR5(-) subsets of alpha4(+)beta7(hi) and beta7(-)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 beta7(-)CD4(+)CCR5(+) and beta7(-)CD4(+)CCR5(-) T cells. alpha4beta7(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 alpha4(+)beta7(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.
authors: Deptartment of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors: M
authors: M
authors: Kader
authors: X
authors: X
authors: Wang
authors: M
authors: M
authors: Piatak
authors: J
authors: J
authors: Lifson
authors: M
authors: M
authors: Roederer
authors: R
authors: R
authors: Veazey
authors: J J
authors: JJ
authors: Mattapallil
mesh_terms: D000208:Acute Disease; D000818:Animals; D018791:CD4 Lymphocyte Count; D054884:Host-Pathogen Interactions / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008253:Macaca mulatta; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D053585:Virus Attachment
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma