Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection

Ester M. M. van Leeuwen, Ester B. M. Remmerswaal, Mirjam H. M. Heemskerk, Ineke J. M. ten Berge, Rene A. W. van Lier

Research output: Contribution to JournalArticleAcademicpeer-review

74 Citations (Scopus)

Abstract

To obtain insight into human CD4+ T cell differentiation and selection in vivo, we longitudinally studied cytomegalovirus (CMV)-specific CD4+ T cells after primary infection. Early in infection, CMV-specific CD4+ T cells have the appearance of interferon gamma (IFNgamma)-producing T-helper 1 (TH1) type cells, whereas during latency a large population of CMV-specific CD4+ CD28- T cells emerges with immediate cytotoxic capacity. We demonstrate that CD4+ CD28- T cells could lyse CMV antigen-expressing target cells in a class II-dependent manner. To clarify the clonal relationship between early and late CMV-specific CD4+ T cells, we determined their Vbeta usage and CDR3 sequences. The T-cell receptor beta (TCRbeta) diversity in the early CMV-specific CD4+ T-cell population was high in contrast to the use of a very restricted set of TCRbeta sequences in latent infection. T-cell clones found in the late CMV-specific CD4+ T-cell population could not be retrieved from the early CD4+ T-cell population, or were present only at a low frequency. The observation that dominant CMV-specific CD4+ clones during latency were only poorly represented in the acute phase suggests that after the initial control of the virus strong selection and/or priming of novel clones takes place in persistent infections in humans
Original languageEnglish
Pages (from-to)3121-3127
JournalBlood
Volume108
Issue number9
DOIs
Publication statusPublished - 2006

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