title: Differential effect of CD69 targeting on bystander and antigen-specific T cell proliferation.
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.
authors.affiliation: Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Alari-Pahissa
authors.forename: Javier
authors.initials: J
authors.lastname: Vega-Ramos
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: A Raúl
authors.initials: AR
authors.lastname: Castaño
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
authors.forename: José A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Pilar
authors.initials: P
authors.lastname: Lauzurica
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D024201:Bystander Effect; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018398:Homeodomain Proteins / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018398:Homeodomain Proteins; D007376:Interleukin-2; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C064658:RAG-1 protein