Journal
CELLULAR IMMUNOLOGY
Volume 259, Issue 2, Pages 177-184Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2009.06.013
Keywords
Costimulation; CD28; ICOS; Follicular B helper T cells; Rodent; Th2 Cells; Antibodies; Allergy; Asthma
Categories
Funding
- NIH [R01 Al50180, P01 Al56352, K08 Al 059105]
- American Lung Association of Metropolitan Chicago and Louis Block Fund
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000055] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI056352, K08AI059105, R01AI050180, U54AI057153] Funding Source: NIH RePORTER
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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. (C) 2009 Elsevier Inc. All rights reserved.
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