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* Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology,
Laboratory for Experimental Immunology,
Emma Children’s Hospital, and
Department of Virology, Academic Medical Center, Amsterdam, The Netherlands
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-
after stimulation with CMV-Ag, whereas CD4+CD28+ cells also produced IFN- 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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