Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation.

Journal article

Efficient T cell activation requires the engagement of a variety of ligand/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activation. The present study dissects the roles of LFA-1 and CD28 in the activation of naive virus-specific CD8+ T cells. We demonstrate that LFA-1 facilitates T cell activation by lowering the amounts of antigen necessary for T cell activation. In the absence of LFA-1, 100-fold more antigen was required for T cell-antigen-presenting cell (APC) conjugation and all subsequent events of T cell activation, including TCR down-regulation, Ca2+-flux, T cell proliferation, and lytic effector cell induction. Thus, LFA-1 facilitates the functional triggering of TCRs by promoting adhesion of T cells to APCs but does not affect T cell activation otherwise. In contrast, CD28 played an entirely different role during T cell activation. CD28 reduced the number of TCRs that had to be triggered for T cell activation and allowed activation of T cells by low affinity ligands. CD28 but not LFA-1 prevented induction of T cell unresponsiveness after stimulation of TCRs. These results demonstrate that LFA-1 and CD28 exhibit distinct, nonoverlapping ways to influence T cell activation and suggest that the terms costimulation and signal 2 should be revisited.

Authors: Bachmann, M; McKall-Faienza, K; Schmits, R; Bouchard, D; Beach, J

• Publication status: Published
• Journal: Immunity
• Volume: 7
• Issue: 4
• Pages: 549-557
• Publication date: 1997-10-01
• DOI: 10.1016/s1074-7613(00)80376-3
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Down-Regulation; Animals; Lymphocytic choriomeningitis virus; Antigens, CD28; Antigens, Viral; Cell Adhesion; Clonal Anergy; Cell Adhesion Molecules; Mice; Interleukin-2; Antigen-Presenting Cells; Receptors, Antigen, T-Cell; Lymphocyte Activation; Peptides; Lymphocyte Function-Associated Antigen-1; Mice, Transgenic; Signal Transduction; T-Lymphocytes; Calcium