CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo.
Previous work has shown ICOS can function independently of CD28, but whether either molecule can compensate for the other in vivo is not known. Since ICOS is a potent inducer of Th2 cytokines and linked to allergy and elevated serum IgE in humans, we hypothesized that augmenting ICOS costimulation in murine allergic airway disease may overcome CD28 deficiency. While ICOS was expressed on T cells from CD28(-/-) mice, Th2-mediated airway inflammation was not induced in CD28(-/-) mice by increased ICOS costimulation. Further, we determined if augmenting CD28 costimulation could compensate for ICOS deficiency. ICOS(-/-) mice had a defect in airway eosinophilia that was not overcome by augmenting CD28 costimulation. CD28 costimulation also did not fully compensate for ICOS for antibody responses, germinal center formation or the development of follicular B helper T cells. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo.
Shilling
Rebecca A
RA
Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, MC6076, Room M658, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. rshillin@medicine.bsd.uchicago.edu
Clay
Bryan S
BS
Tesciuba
Amanda G
AG
Berry
Elizabeth L
EL
Lu
Tiffany
T
Moore
Tamson V
TV
Bandukwala
Hozefa S
HS
Tong
Jiankun
J
Weinstock
Joel V
JV
Flavell
Richard A
RA
Horan
Tom
T
Yoshinaga
Steve K
SK
Welcher
Andrew A
AA
Cannon
Judy L
JL
Sperling
Anne I
AI
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006651:Histocytochemistry; D007111:Immunity, Cellular / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D060889:Inducible T-Cell Co-Stimulator Protein; D008171:Lung Diseases / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007073:Immunoglobulin E