title: Properties of CD4(+) T cells in human cytomegalovirus infection.
abstract: The correlates of protective immunity to disease-inducing viruses in man remain to be elucidated. We determined the kinetics and properties of cytomegalovirus (CMV)-specific CD4(+) T cells in healthy individuals and renal transplant recipients during different stages of CMV infection. Our data reveal that circulating CMV-specific CD4(+) T cells displayed an effector-memory phenotype, and produced the T helper 1 cytokines interferon-gamma and tumor necrosis factor-alpha. In addition, they lacked molecules for secondary lymphoid organ homing and expressed the cytotoxic molecule granzyme B, inferring a direct role of these cells at target sites of infection. In asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, whereas in symptomatic individuals the CMV-specific effector memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T cell and antibody responses are insufficient to control viral replication and that formation of effector memory CD4(+) T cells is necessary for recovery of infection.
authors.affiliation: Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. L.E.Granadia@amc.uva.nl
authors.forename: Laila E
authors.initials: LE
authors.lastname: Gamadia
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Rentenaar
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000378:metabolism; D040881:CD11a Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology*; D004279:DNA, Viral; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D039441:Integrin alpha4 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects; D019041:L-Selectin / Q000378:metabolism; D008137:Longitudinal Studies; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load; D017735:Virus Latency / Q000187:drug effects / Q000276:immunology
chemical_list: D015703:Antigens, CD; C515370:CCR7 protein, human; D040881:CD11a Antigen; D004279:DNA, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D039441:Integrin alpha4; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases