Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adjuvants, Immunologic / physiology*
-
Animals
-
B-Cell Activating Factor
-
B-Lymphocytes / immunology
-
B-Lymphocytes / metabolism
-
B-Lymphocytes / pathology
-
Dose-Response Relationship, Immunologic
-
Epitopes, T-Lymphocyte / administration & dosage
-
Epitopes, T-Lymphocyte / immunology
-
Hypersensitivity, Delayed / genetics
-
Hypersensitivity, Delayed / immunology
-
Hypersensitivity, Delayed / pathology
-
Immune Tolerance / genetics
-
Immunologic Memory / genetics
-
Inflammation Mediators / blood
-
Inflammation Mediators / metabolism
-
Inflammation Mediators / physiology*
-
Injections, Intradermal
-
Interferon-gamma / biosynthesis
-
Lymph Nodes / immunology
-
Lymph Nodes / metabolism
-
Lymphocyte Activation / genetics
-
Lymphocyte Activation / immunology
-
Lymphocyte Count
-
Membrane Proteins / blood
-
Membrane Proteins / deficiency
-
Membrane Proteins / genetics
-
Membrane Proteins / physiology*
-
Mice
-
Mice, Knockout
-
Mice, Transgenic
-
Ovalbumin / administration & dosage
-
Ovalbumin / immunology
-
Respiratory Hypersensitivity / genetics
-
Respiratory Hypersensitivity / immunology
-
Respiratory Hypersensitivity / pathology
-
Respiratory Hypersensitivity / prevention & control
-
Serum Albumin, Bovine / administration & dosage
-
Serum Albumin, Bovine / immunology
-
Th1 Cells / immunology*
-
Th1 Cells / metabolism
-
Th1 Cells / pathology*
-
Th2 Cells / immunology
-
Th2 Cells / metabolism
-
Tumor Necrosis Factor-alpha / deficiency
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / physiology*
Substances
-
Adjuvants, Immunologic
-
B-Cell Activating Factor
-
Epitopes, T-Lymphocyte
-
Inflammation Mediators
-
Membrane Proteins
-
Tnfsf13b protein, mouse
-
Tumor Necrosis Factor-alpha
-
methylated bovine serum albumin
-
Serum Albumin, Bovine
-
Interferon-gamma
-
Ovalbumin