Interleukin-1 beta, but not interleukin-1 alpha, is required for T-cell-dependent antibody production.
Interleukin-1 (IL-1) consists of two molecules, IL-1 alpha and IL-1 beta, and IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of these molecules. Although the adjuvant effects of exogenously administered IL-1 in the humoral immune response are well known, the roles of endogenous IL-1 and the functional discrimination between IL-1 alpha and IL-1 beta have not been elucidated completely. In this report, we investigated the role of IL-1 in the humoral immune response using gene-targeted mice. Both primary and secondary antibody production against T-dependent antigen, sheep red blood cells (SRBC), was significantly reduced in IL-1 alpha/beta-/- mice, and was enhanced in IL-1Ra-/- mice. The intrinsic functions of B cells, such as antibody production against type 1 T-independent antigen, trinitrophenyl-lipopolysaccharide and proliferative responses against mitogenic stimuli, were normal in IL-1 alpha/beta-/- mice. The proliferative response of T cells and cytokine production upon stimulation with anti-CD3 monoclonal antibody were also normal, as was the phagocytotic ability of antigen-presenting cells (APCs). However, SRBC-specific proliferative response and cytokine production of T cells through the interaction with APCs were markedly impaired in IL-1 alpha/beta-/- mice, and enhanced in IL-1Ra-/- mice. Moreover, we show that SRBC-specific antibody production was reduced in IL-1 beta-/- mice, but not in IL-1 alpha-/- mice. These results show that endogenous IL-1 beta, but not IL-1 alpha, is involved in T-cell-dependent antibody production, and IL-1 promotes the antigen-specific T-cell helper function through the T-cell-APC interaction.
Nakae
S
S
Centre for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Asano
M
M
Horai
R
R
Iwakura
Y
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007375:Interleukin-1; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D005362:Ficoll