Differential effect of CD69 targeting on bystander and antigen-specific T cell proliferation

Elisenda Alari-Pahissa, Javier Vega-Ramos, Jian Guo Zhang, A. Raúl Castaño, Shannon J. Turley, José A. Villadangos, Pilar Lauzurica

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12 Citations (Scopus)

Abstract

In spite of an initially proposed role as a costimulatory molecule for CD69, in vivo studies showed it as a regulator of immune responses and lymphocyte egress. We found constitutive CD69 expression by T cell subsets and pDC. We examined a possible effect of CD69 on T cell proliferation using transfer models and in vitro assays. In mice locally expressing or receiving antigen, anti-CD692.2 treatment did not affect the proliferation of antigen-specific transgenic T cells in ADLN, although we observed the presence of proliferated T cells in non-ADLN and spleen. This was not affected by FTY720 treatment and thus, not contributed by increased egress of proliferated lymphocytes from ADLN. In the absence of antigen, anti-CD69 2.2 treatment induced bystander proliferation of transferred memory pheno-type T cells. This proliferation was mediated by IL-2, as it was inhibited by anti-IL-2 or anti-CD25 antibodies in vitro and by anti-CD25 antibodies in vivo. It was also dependent on CD69 expression by donor T cells and recipient cells. CD69 targeting on T cells enhanced IL-2-mediated proliferation and CD25 expression. However, it did not lead to increased early IL-2 production by T cells. No T cell subset was found to be specifically required in the recipient. Instead, CD69 targeting on pDC induced their expression of IL-2 and CD25, and pDC depletion showed that this subset was involved in the proliferation induction. These results indicate that CD69 targeting induces bystander T cell proliferation through pDC IL-2 production and T cell sensitization to IL-2 without affecting antigen-driven T cell proliferation. © Society for Leukocyte Biology.
Original languageEnglish
Pages (from-to)145-158
Number of pages14
JournalJournal of Leukocyte Biology
Volume92
Issue number1
DOIs
Publication statusPublished - 1 Jul 2012

Keywords

  • Cell proliferation
  • Dendritic cell
  • Rodent
  • Transgenic/knockout mice

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