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Allergic humans are hypo‐responsive to CXCR3 chemokines in a Th1 immunity‐promoting loop
Author(s) -
Campbell Darren,
Gangur Venu,
Simons F. Estelle R.,
HayGlass Kent T.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0908fje
Subject(s) - cxcr3 , immunology , chemokine , cxcl10 , peripheral blood mononuclear cell , allergic response , t cell , chemistry , biology , chemokine receptor , immune system , immunoglobulin e , in vitro , biochemistry , antibody
CXCR3 binding chemokine CXCL10 (IP‐10) markedly enhances antigen‐specific Th1 recall responses in healthy humans, suggesting a role for this pathway in maintenance of clinical tolerance to environmental allergens as well as a potential therapeutic role for CXCR3 ligands in re‐balancing the Th2‐dominated responses that underlie generation and maintenance of allergic disorders. Here, we investigated the capacity of CXCR3 ligands to modulate allergen‐driven IFNγ production by healthy and allergic individuals characterized by Th1 and Th2 immunity‐ dominated allergen specific responses, respectively. Exogenous CXCR3 ligands up‐regulated antigen‐dependent IFNγ production from healthy individuals' peripheral blood mononuclear cells up to 120‐fold, a response neutralized by anti‐CXCR3 treatment and not emulated by CCR5 ligands. In contrast, allergic individuals were strikingly hypo‐responsive to CXCR3 ligands ( P =0.0004). Chemokine‐enhanced IFNγ production correlated with T cell CXCR3 expression (r=0.736, P =0.0001) in vivo and was independent of Th2 cytokine levels. These findings demonstrate that CXCR3‐ligation preferentially augments ongoing Th1 over Th2 responses and suggest that reduced capacity of allergic individuals to respond to CXCR3 ligands promotes the maintenance of human allergic disorders.