Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naIve CD4~+ T cells

摘要

The mechanisms controlling induction of anergy at the level of naive CD4~+ T cells are poorly understood but thought to reflect limited contact with costimulatory molecules during T cell antigen receptor (TCR) ligation. To clarify this question, naive TCR trans- genic CD4~+ cells were exposed to specific peptide presented by transfected antigen-presenting cells (APC) expressing MHC class Ⅱ molecules with defined accessory molecules. Significantly, cultur- ing CD4~+ cells with APC expressing MHC Ⅱ plus peptide alone elicited early TCR signaling but failed to induce either proliferation or anergy. Culture with APC expressing MHC ll plus B7 molecules led to strong proliferation and T cell priming but no anergy. In marked contrast, conspicuous induction of anergy occurred after T cell culture with APC expressing MHC class Ⅱ and intercellular adhesion molecule-1 (ICAM-1). Thus, at the level of naive CD4~+ cells, anergy induction appears to reflect selective contact with APC expressing ICAM-1 in the absence of B7.