Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection.
Cytotoxic CD4(+)CD28(-) T cells form a rare subset in human peripheral blood. The presence of CD4(+)CD28(-) cells has been associated with chronic viral infections, but how these particular cells are generated is unknown. In this study, we show that in primary CMV infections, CD4(+)CD28(-) T cells emerge just after cessation of the viral load, indicating that infection with CMV triggers the formation of CD4(+)CD28(-) T cells. In line with this, we found these cells only in CMV-infected persons. CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin. Importantly, CD4(+)CD28(-) cells were to a large extent CMV-specific because proliferation was only induced by CMV-Ag, but not by recall Ags such as purified protein derivative or tetanus toxoid. CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative. Thus, CD4(+)CD28(-) T cells emerge as a consequence of CMV infection.
van Leeuwen
Ester M M
EM
Department of Internal Medicine, and Laboratory of for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. E.M.vanLeeuwen@amc.uva.nl
Remmerswaal
Ester B M
EB
Vossen
Mireille T M
MT
Rowshani
Ajda T
AT
Wertheim-van Dillen
Pauline M E
PM
van Lier
René A W
RA
ten Berge
Ineke J M
IJ
D000956:Antigens, Viral / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003289:Convalescence; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D053804:Granzymes; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011183:Postoperative Complications / Q000276:immunology / Q000821:virology; D012697:Serine Endopeptidases / Q000032:analysis; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D019562:Viral Load
D000956:Antigens, Viral; D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D013745:Tetanus Toxoid; D014373:Tuberculin; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases