Anti-lymphocyte function associated antigen-1 inhibits T-helper 2 function of human allergen-specific CD4+ T cells.

Abstract

Blockade of lymphocyte function associated antigen-1 (LFA-1) is proving successful in the management of psoriasis and other inflammatory skin conditions including atopic dermatitis (AD), but the dependence of allergen-specific CD4+ T-cell function on LFA-1 has not been studied extensively. We sought to investigate the potential ability of LFA-1 inhibition to influence keratinocyte presentation of allergen to specific T-helper (Th) 2 cell clones. Using human leucocyte antigen class II tetrameric complexes, we generated Der p 1-specific DRB1*1501-restricted CD4+ T-cell lines (n=5) and clones (n=4) from the peripheral blood of five adults with AD. Using doses of anti-LFA-1 present in vivo, we observed significant inhibition (P<0.05) of allergen-specific CD4+ T-cell production of interleukin-4 with such inhibition occurring during presentation of allergen by keratinocytes. These data show that at doses present in vivo, LFA-1 blockade inhibits keratinocyte presentation to allergen-specific Th2 cells, suggesting one mechanism through which anti-LFA-1 may be beneficial therapeutically.