S. Nakae et al., Interleukin-1 beta, but not interleukin-1 alpha, is required for T-cell-dependent antibody production, IMMUNOLOGY, 104(4), 2001, pp. 402-409
Interleukin-1 (IL-1) consists of two molecules, IL-1 alpha and IL-1 beta, a
nd IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of these molecu
les. Although the adjuvant effects of exogenously administered IL-1 in the
humoral immune response are well known, the roles of endogenous IL-I and th
e functional discrimination between IL-1 alpha and IL-1 beta have not been
elucidated completely. In this report, we investigated the role of IL-I in
the humoral immune response using gene-targeted mice. Both primary and seco
ndary antibody production against T-dependent antigen, sheep red blood cell
s (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 a
ntibody production against type 1 T-independent antigen, trinitrophenyl-lip
opolysaccharide and proliferative responses against mitogenic stimuli, were
normal in IL-1 alpha/beta (-/-) mice. The proliferative response of T cell
s and cytokine production upon stimulation with anti-CD3 monoclonal antibod
y were also normal, as was the phagocytotic ability of antigen-presenting c
ells (APCs). However, SRBC-specific proliferative response and cytokine pro
duction 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 mice, but no
t in IL-1 alpha (-/-) mice. These results show that endogenous IL-1 beta, b
ut 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-ce
ll-APC interaction.