title: Human cytomegalovirus particles directly suppress CD4 T-lymphocyte activation and proliferation.
abstract: CD4 T cells are important regulators of the immune system and are vital for mounting a strong immune response against viral infections. Human cytomegalovirus (HCMV) is known to be a strong modulator of the innate as well as adaptive immune responses. In this study, we found that HCMV directly inhibited proliferation of CD4 T cells and rendered them unresponsive to immunological stimuli. This effect was not observed when CD4 T cells were treated with herpes simplex virus-1/2 or measles virus. When stimulated with phytohemagglutinin, concanavalin A, or phorbol myristate acetate, HCMV-treated T cells were unable to proliferate, revealing an ability of HCMV to inhibit CD4 T cell response. Furthermore, HCMV also prevented proliferation of leukemic T-cell lines. HCMV-treated CD4 T cells expressed the activation markers CD45RO and CD69, were not apoptotic and produced decreased levels of the cytokines IL-4, IFN-γ and TNF-α, compared to untreated controls. The inhibitory effect of HCMV on CD4 T cell proliferation was not mediated by HCMV gH, gB or other immunogenic glycoproteins, since intravenous immunoglobulins or gB- or gH-specific neutralizing antibodies did not prevent the suppression of T-cell proliferation. Our observations show that HCMV inhibits CD4 T cell function with potential clinical consequences for both humoral and cell-mediated immune responses.
authors: Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, 17176 Stockholm, Sweden.
authors: Olesja
authors: O
authors: Fornara
authors: Jenny
authors: J
authors: Odeberg
authors: Zahidul
authors: Z
authors: Khan
authors: Giuseppe
authors: G
authors: Stragliotto
authors: Inti
authors: I
authors: Peredo
authors: Lynn
authors: L
authors: Butler
authors: Cecilia
authors: C
authors: Söderberg-Nauclér
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003208:Concanavalin A; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D020014:K562 Cells; D037181:Lectins, C-Type / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008459:Measles virus / Q000276:immunology; D010835:Phytohemagglutinins; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099192:CD69 Antigens
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003208:Concanavalin A; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D010835:Phytohemagglutinins; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens