title: HIV infection of primary CD4+ Th2 cells, defined by expression of the chemoattractant receptor-homologous (CRTH2), induces a Th0 phenotype.
abstract: The association between HIV, cytokine profile, and disease progression is controversial. In this study, we evaluated whether HIV infection of a primary T helper-like type 2 cytokine (Th2) cell subset augments their cytokine profile. We utilized the CRTH2 (chemoattractant receptor-homologous) marker to identify CD4+ Th2 cells. Approximately 2-4% of CD4+ T cells are CRTH2+. CRTH2+ expression is confirmed to delineate a Th2 subset as indicated by robust inducible IL-4 response. CD4+ CRTH2+ T cells were also more inherently activated than their CRTH2-negative counterpart as indicated by a higher percent expression of CD69, CD45RO, CD95, CD25, and HLA-DR. CD4+CRTH2+ T cells were not terminally differentiated as indicated by expression of CD27 and CD28. In vitro HIV infection of primary human CD4 CRTH2T cells, independent of chemokine coreceptor usage, potently upregulated IFN-gamma production while still maintaining robust IL-4 expression. This Th0 (IFNgamma+ IL-4+) phenotype was upregulated in CD4+CRTH2+ T cells post-HIV infection by 18-fold, demonstrating a shift to a Th0 phenotype. Ex vivo studies also demonstrated that HIV+ patients exhibited a decline in CD4+CRTH2+ cells and a shift of this population toward cells that express both IFN-gamma and IL-4. Collectively, these data indicate that HIV replication in Th2 cells induces a Th0 phenotype. This phenomenon may be a deliberate viral escape mechanism to prevent the skewing of the immune response toward Th1 or Th2.
authors.affiliation: Department of Immunology/Microbiology , Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA.
authors.forename: Bouchaib
authors.initials: B
authors.lastname: Bahbouhi
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Allan
authors.initials: A
authors.lastname: Tenorio
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000821:virology; D018418:Th2 Cells / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; C508598:IL4 protein, human; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015847:Interleukin-4; D007371:Interferon-gamma; C036293:prostaglandin D2 receptor