title: A Th0/Th2-like function of CD4+CD7- T helper cells from normal donors and HIV-infected patients.
abstract: We previously reported the expansion during HIV infection of a subset of CD4+ T cells characterized by a lack of CD7 cell surface expression. This CD4+CD7- subset showed in normal donors a lower cell proliferation than CD4+CD7+ autologous cells after CD3 triggering or CD28 costimulation. Our aim was to further characterize the Th function of this CD4+CD7- T cell subset, both in normal donors and in HIV-infected patients. Their CD4+CD7- cell proliferation and cytokine secretion were analyzed after cell-sorting and co-stimulation of the CD3 and CD28 pathways. In normal donors, the IL-2 produced by CD4+CD7- cells in response to a CD3 plus CD28 costimulus represented 50 +/- 28% of the autologous CD4+CD7+ cell IL-2 secretion. In addition, the CD4+CD7+ T cells produced higher amounts of IL-4 and IL-10 than the CD4+CD7+ cells with mean CD4+CD7-: CD4+CD7+ ratios of 5.4 +/- 4.5 and 26 +/- 25, for IL-4 and IL-10, respectively, whereas the IFN-gamma production was similar in both subsets. After a triggering of the CD3 complex alone, significant amounts of IL-2 were detectable in CD4+CD7+ cell supernatants only; conversely, IL-4 and IL-10 could be detected only in the culture medium from CD4+CD7- T cells. This profile of cytokine production was maintained both over time and at the clonal cell level in the CD4+CD7- T cell subset. In HIV-infected patients, the CD4+CD7- T cell expansion observed in relationship with disease progression was associated to an in vivo activation of the CD4+CD7- cells, as assessed by cell surface expression of the HLA-DR, CD25, CD71, and CD57 markers. The CD4+CD7- T cells from HIV-seropositive patients showed the same imbalance of cell proliferation and IL-2, IL-4, and IL-10 production as observed in normal donors despite low levels of proliferation and cytokine production. Together, our data indicate that the lack of CD7 expression defines a CD4+ Th cell subset with a Th0/Th2-like profile of cytokine secretion in normal individuals. The CD4+CD7- subset is expanded during HIV infection and characterized by the same although impaired profile of cytokine production. These CD4+CD7- T cells might play a role in the Th cell dysfunctions observed in HIV infection.
authors.affiliation: Laboratory of Cellular and Tissue Immunology, CNRS URA625, Hospital Pitié-Salpétrière, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Autran
authors.forename: E
authors.initials: E
authors.lastname: Legac
authors.forename: C
authors.initials: C
authors.lastname: Blanc
authors.forename: P
authors.initials: P
authors.lastname: Debré
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D012016:Reference Values; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4