Differential effect of CD69 targeting on bystander and antigen-specific T cell proliferation
- Author(s)
- Alari-Pahissa, E; Vega-Ramos, J; Zhang, JG; Castano, AR; Turley, SJ; Villadangos, JA; Lauzurica, P;
- Details
- Publication Year 2012-07,Volume 92,Issue #1,Page 145-158
- Journal Title
- JOURNAL OF LEUKOCYTE BIOLOGY
- Publication Type
- Journal Article
- 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 phenotype 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. J. Leukoc. Biol. 92: 145-158; 2012.
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Keywords
- COLLAGEN-INDUCED ARTHRITIS; IN-VIVO; DENDRITIC CELLS; SELECTIVE STIMULATION; MONOCLONAL-ANTIBODY; LYMPHOCYTE EGRESS; IL-2 PRODUCTION; ACTIVATION; RECEPTOR; EXPRESSION
- Research Division(s)
- Immunology; Cancer And Haematology
- Publisher's Version
- https://doi.org/10.1189/jlb.1011499
- Terms of Use/Rights Notice
- © 2012 Society for Leukocyte Biology
Creation Date: 2012-07-01 12:00:00
Last Modified: 2014-12-05 12:15:03