title: Identification of a CCR5-expressing T cell subset that is resistant to R5-tropic HIV infection.
abstract: Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4(+) memory and naïve T cells during HIV-1 infection, we found that a subset of CD4(+) effector memory T cells that are CCR7(-)CD45RO(-)CD45RA(+) (referred to as TEMRA cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high levels of CCR5, TEMRA cells were strikingly resistant to infection with CCR5 (R5)-tropic HIV-1, but remained highly susceptible to CXCR4 (X4)-tropic HIV-1. The resistance of TEMRA cells to R5-tropic viruses was determined to be post-entry of the virus and prior to early viral reverse transcription, suggesting a block at the uncoating stage. Remarkably, in a subset of the HIV-infected individuals, the relatively high proportion of TEMRA cells within effector T cells strongly correlated with higher CD4(+) T cell numbers. These data provide compelling evidence for selection of an HIV-1-resistant CD4(+) T cell population during the course of HIV-1 infection. Determining the host factors within TEMRA cells that restrict R5-tropic viruses and endow HIV-1-specific CD4(+) T cells with this ability may result in novel therapeutic strategies against HIV-1 infection.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, Tennessee, United States of America.
authors.forename: Kyra
authors.initials: K
authors.lastname: Oswald-Richter
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Grill
authors.forename: Mindy
authors.initials: M
authors.lastname: Leelawong
authors.forename: Michelle
authors.initials: M
authors.lastname: Tseng
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002455:Cell Division / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
chemical_list: D016915:AIDS Vaccines; C515370:CCR7 protein, human; D017252:CD3 Complex; D015704:CD4 Antigens; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens