Both LFA‐1‐positive and ‐deficient T cell clones require the CD2/LFA‐3 interaction for specific cytolytic activation

摘要

AbstractWe investigated the capacity of T lymphocytes from a leukocyte adhesion‐deficient (LAD) patient to respond to alloantigen. Leukocytes of this patient completely lacked LFA‐1 surface expression due to the absence of mRNA coding for theLFA‐1 β chain. Despite the absence of LFA‐1, T lymphocytes obtained from this patient, cultured with allogeneic stimulator cells (lymphoblastoid B cells JY), were capable of lysing JY cells. Furthermore, two T cell clones (one CD4+and one CD8+), generated from this lymphocyte culture, specifically lysed theallogeneic lymphoblastoid JY cells. The cytolytic capacity of LFA‐1‐negative T lymphocytes and T cell clones was comparable to that of control LFA‐1‐positive T cells with allospecificity against JY. Detailed analysis of the CD4 positive and LFA‐1‐negative T cell clone demonstrated that it specifically recognized HLA‐DQ. Antibody inhibition studies showed that the CTL/target cell interaction was mediated through the CD2/LFA‐3 adhesion pathway. LFA‐1 expressed by the target cells did not participate in the CTL/target cell conjugate formation and contributed only minimally to the cytotoxic activity. Moreover, when allogeneic LFA‐1‐deficient B cells, bearingthe appropriate HLA‐DQ alloantigen, were used as target cells, significant levels of specific cytotoxicity were measured, further excluding a role for LFA‐1 in this interaction. The adhesion molecules, VLA‐4, CD44 and L‐selectin (LECAM1) were not involved.These results demonstrate that LFA‐1‐negative T lymphocytes can exert allospecific cytotoxicity and that CTL/target cell contact is mediated through the CD2/LFA‐3 route. This observation may explain in part why in LAD patients viralinfections, cleared largely by T cells, are less frequently observed than bacterial infections,