High avidity TCR-peptide interactions between CD4 lymphocytes and lymph node dendritic cells promote normal lymphocyte arrest, activation, proliferation, and differentiation independently of dendritic cell ICAM-1 and 2

Abstract

Abstract The two main LFA-1 ligands ICAM-1 and ICAM-2 are constitutively co-expressed on antigen presenting cells (APCs) and on the lymph node stroma. We find abrogated antigen specific CD4 T cell priming in ICAM-1 and ICAM-2 deficient spleens. Nevertheless, the in vivo contribution of these ligands to lymphocyte activation proliferation and differentiation in lymph nodes has been difficult to dissect in total knockout mice due to their multiple roles in lymphocyte entry and priming in these organs. We therefore constructed lethally irradiated chimeric mice reconstituted with ICAM-1 and 2 double knock out (DKO) APCs in which lymphocyte entry into peripheral lymph nodes was reconstituted. Strikingly, these mice elicited normal antigen specific OT-II T cell activation, proliferation and differentiation into Th1 and Tfh effectors. OT-II T cells could also normally arrest on DCs deficient in ICAM-1 and 2. A compensatory role of VCAM-1 in ICAM deficient DCs was ruled out. Nevertheless, polyclonal T cell proliferation in response to endogenous self-antigens required the presence of ICAM-1 and ICAM-2 on endogenous lymph node DCs. Our results are the first indication that high avidity TCR peptide-MHC-II recognition can bypass integrin-mediated lymphocyte adhesions to DCs under specific settings.