Human cytomegalovirus particles directly suppress CD4 T-lymphocyte activation and proliferation

TY - JOUR

T1 - Human cytomegalovirus particles directly suppress CD4 T-lymphocyte activation and proliferation

AU - Fornara, Olesja

AU - Odeberg, Jenny

AU - Khan, Zahidul

AU - Stragliotto, Giuseppe

AU - Peredo, Inti

AU - Butler, Lynn

AU - Söderberg-Nauclér, Cecilia

N1 - Copyright © 2013 Elsevier GmbH. All rights reserved.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Antibodies, Viral

KW - Antigens, CD

KW - Antigens, CD45

KW - Antigens, Differentiation, T-Lymphocyte

KW - CD4-Positive T-Lymphocytes

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Concanavalin A

KW - Cytomegalovirus

KW - Cytomegalovirus Infections

KW - Herpesvirus 1, Human

KW - Herpesvirus 2, Human

KW - Humans

KW - Interferon-gamma

KW - Interleukin-4

KW - K562 Cells

KW - Lectins, C-Type

KW - Leukocytes, Mononuclear

KW - Lymphocyte Activation

KW - Macrophages

KW - Measles virus

KW - Phytohemagglutinins

KW - Tetradecanoylphorbol Acetate

KW - Tumor Necrosis Factor-alpha

U2 - 10.1016/j.imbio.2013.01.002

DO - 10.1016/j.imbio.2013.01.002

M3 - SCORING: Journal article

C2 - 23434301

VL - 218

SP - 1034

EP - 1040

JO - IMMUNOBIOLOGY

JF - IMMUNOBIOLOGY

SN - 0171-2985

IS - 8

ER -