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.
- Cell proliferation
- Dendritic cell
- Transgenic/knockout mice
Alari-Pahissa, E., Vega-Ramos, J., Zhang, J. G., Raúl Castaño, A., Turley, S. J., Villadangos, J. A., & Lauzurica, P. (2012). Differential effect of CD69 targeting on bystander and antigen-specific T cell proliferation. Journal of Leukocyte Biology, 92(1), 145-158. https://doi.org/10.1189/jlb.1011499, https://doi.org/10.1189/jlb.1011499