BAFF augments certain Th1-associated inflammatory responses.
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.
Sutherland
Andrew P R
AP
Arthritis and Asthma Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Ng
Lai Guan
LG
Fletcher
Carrie A
CA
Shum
Bennett
B
Newton
Rebecca A
RA
Grey
Shane T
ST
Rolph
Michael S
MS
Mackay
Fabienne
F
Mackay
Charles R
CR
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000276:Adjuvants, Immunologic; D053264:B-Cell Activating Factor; D018984:Epitopes, T-Lymphocyte; D018836:Inflammation Mediators; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma; D010047:Ovalbumin