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Comparative Study
. 2004 Aug 1;173(3):1834-41.
doi: 10.4049/jimmunol.173.3.1834.

Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection

Ester M M van Leeuwen  1 , Ester B M Remmerswaal, Mireille T M Vossen, Ajda T Rowshani, Pauline M E Wertheim-van Dillen, René A W van Lier, Ineke J M ten Berge
Affiliations
Comparative Study

Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection

Ester M M van Leeuwen et al. J Immunol. .

Abstract

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.

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