IL-1 enhances T cell-dependent antibody production through induction of CD40 ligand and OX40 on T cells.
IL-1 is a proinflammatory cytokine that plays pleiotropic roles in host defense mechanisms. We investigated the role of IL-1 in the humoral immune response using gene-targeted mice. Ab production against SRBC was significantly reduced in IL-1alpha/beta-deficient (IL-1(-/-)) mice and enhanced in IL-1R antagonist(-/-) mice. The intrinsic functions of T, B, and APCs were normal in IL-1(-/-) mice. However, we showed that IL-1(-/-) APCs did not fully activate DO11.10 T cells, while IL-1R antagonist (-/-) APCs enhanced the reaction, indicating that IL-1 promotes T cell priming through T-APC interaction. The function of IL-1 was CD28-CD80/CD86 independent. We found that CD40 ligand and OX40 expression on T cells was affected by the mutation, and the reduced Ag-specific B cell response in IL-1(-/-) mice was recovered by the treatment with agonistic anti-CD40 mAb both in vitro and in vivo. These observations indicate that IL-1 enhances T cell-dependent Ab production by augmenting CD40 ligand and OX40 expression on T cells.
Nakae
S
S
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Asano
M
M
Horai
R
R
Sakaguchi
N
N
Iwakura
Y
Y
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000502:physiology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012756:Sheep; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand