B7-2 requirement for helminth-induced granuloma formation and CD4 type 2 T helper cell cytokine expression.
B7 ligands on APCs engage CD28/CTLA4 counter-receptors on T cells critical for T lymphocyte activation and functional differentiation of T helper subsets. To examine whether the ligands B7-1 (CD80) and B7-2 (CD86) affect gene expression of Th2 cytokines and development of Th2-mediated pathologic tissue reactions, mice were treated with anti-B7-1 or anti-B7-2 at the time of sensitization to footpad inoculation of Schistosoma mansoni eggs or induction of pulmonary granuloma by i.v. injected eggs. Anti-B7-2 treatment inhibited pulmonary granuloma formation by 74% and decreased levels of lung IL-5 and IL-13 transcripts compared with those in animals given control Ig by 20- and 5-fold, respectively, while anti-B7-1 administration has no effect. Anti-B7-2 treatment blocked CD4 cell gene expression of IL-4, IL-5, and IL-13, but had no effect on IFN-gamma or IL-10 in animals inoculated with S. mansoni ova, larvae from the filarial helminth Brugia malayi, or CFA. Anti-B7-1 administration had no effect on CD4 cell transcript levels of IL-4 and IL-5, but inhibited IFN-gamma in mice inoculated with ova. Similar effects of anti-B7-2 on CD4 cell cytokine expression were observed in IL-4 knockout mice, indicating the existence of an alternative pathway for induction and/or expression of these cytokine genes. These findings suggest a possible role for anti-B7-2 in the therapy of infectious and atopic diseases in which immunopathologic reactions are mediated by selected Th2 cytokines.
Subramanian
G
G
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Kazura
J W
JW
Pearlman
E
E
Jia
X
X
Malhotra
I
I
King
C L
CL
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006099:Granuloma / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008174:Lung Diseases, Parasitic / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012552:Schistosomiasis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D015704:CD4 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D007371:Interferon-gamma