Intercellular adhesion molecule-1/leukocyte function associated antigen-1 blockade inhibits alloantigen specific human T cell effector functions without inducing anergy

Background Intercellular adhesion molecule (ICAM-1) is important in leukocy te adhesion-dependent events and some data suggest that ICAM-1 provides T c ell costimulation. We anlayzed the role of the ICAM-1 and leukocyte functio n associated antigen-1 (LFA-1) interaction in human T cell alloreactivity i n vitro. Methods. Allo-antigen-induced T cell proliferation and cytotoxic T lymphocy te lytic activity were assessed by mixed lymphocyte reaction assay and 51 C hromium release assay, respectively. Immunostaining and flow cytometry were used to assess the expression of receptors on activated T cells. Results. Alloantigen-induced T cell proliferation and cytotoxic T lymphocyt e activity were markedly inhibited by antibodies to ICAM-1 and LFA-1, These antibodies had to be present at the time of initial T cell receptor/antige n engagement to inhibit proliferation, Neither IL-2 nor IL-4 were involved in the observed inhibition by antibodies. Inhibition was not associated wit h altered cell surface expression of receptors such as CD3, CD4, ICAM-1, LF A-1, CD25, and HLA-DR however, these antibodies did impede the ability of g eneration of functionally active T cells. Interestingly, these antibodies i nhibited soluble, but not immobilized OKT3-induced proliferation of periphe ral blood leukocytes, Antibody-mediated inhibition of proliferation failed to impair the ability of T cells to subsequently proliferate in response to stimulation by the original or third party alloantigen or mobilize [Ca+ +] (i) in response to CD3 or LFA-1 receptor ligation. Conclusions, These data demonstrate that blockade of ICAM-1/LFA-1 binding a t the time of allorecognition potently blocks initial T cell effector funct ions that could be due to lack of effective T cell/APC engagement.