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The Journal of Immunology, 2005, 174: 5537-5544.
Copyright © 2005 by The American Association of Immunologists

BAFF Augments Certain Th1-Associated Inflammatory Responses1

Andrew P. R. Sutherland2,*, Lai Guan Ng2,*, Carrie A. Fletcher*, Bennett Shum*,{dagger}, Rebecca A. Newton*, Shane T. Grey*, Michael S. Rolph*,{dagger}, Fabienne Mackay*,{dagger} and Charles R. Mackay3,*,{dagger}

* Arthritis and Asthma Research Program, Garvan Institute of Medical Research, Sydney, Australia; and {dagger} Cooperative Research Center for Asthma, Sydney, Australia

B cell-activating factor belonging to the TNF family (BAFF; BLyS) is a critical regulator of B cell maturation and survival, and its overexpression in BAFF transgenic (Tg) mice results in the development of autoimmune disorders. BAFF also affects T cell function through binding to one of the BAFF receptors, BAFF-R. Using BAFF Tg mice, we examined a typical Th1-mediated response, the cutaneous delayed-type hypersensitivity reaction, and found a much greater degree of paw swelling and inflammation than in control mice. Importantly, delayed-type hypersensitivity scores correlated directly with BAFF levels in serum. Conversely, in a Th2-mediated model of allergic airway inflammation, BAFF Tg mice were largely protected and showed markedly reduced Ag-specific T cell proliferation and eosinophil infiltration associated with the airways. Thus, local and/or systemically distributed BAFF affects Th1 and Th2 responses and impacts on the course of some T cell-mediated inflammatory reactions. Our results are consistent with the idea that BAFF augments T cell as well as B cell responses, particularly Th1-type responses. Results in BAFF Tg mice may reflect the situation in certain autoimmune patients or virally infected individuals, because BAFF levels in blood are comparable.




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