LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production.
The role of CD28/B7 and LFA-1/ICAM costimulation in proliferation and Th1/Th2 differentiation of naive CD4+ T cells was addressed using T cells from DO11.10 TCR transgenic mice stimulated by dendritic cells. The blockade of either CD28/B7 or LFA-1/ICAM interactions partially inhibited T cell proliferation. By comparison, blocking CD28/B7 costimulation inhibited IL-4 and IL-5 (Th2 cytokine) production, whereas blocking LFA-1/ICAM-1 or LFA-1/ICAM-2 led to a significant increase (15- to 40-fold) of Th2 cytokines. The combination of anti-ICAM-1 and anti-ICAM-2 mAbs had a synergistic effect with a 100- to 1000-fold increase of Th2 cytokine production. Thus, these two costimulatory pathways have opposing roles in the regulation of Th2 development.
Salomon
B
B
Department of Pathology, Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
Bluestone
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JA
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology; D018106:CD28 Antigens / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1