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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ardern-Jones
M R
MR
MRC Human Immunology Unit, University of Oxford, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK.
Black
A P
AP
Ogg
G S
GS
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D015603:Keratinocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D011565:Psoriasis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015704:CD4 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D015847:Interleukin-4; C472181:efalizumab