Enhancement of T helper2 response in the absence of interleukin (IL-)6; an inhibition of IL-4-mediated T helper2 cell differentiation by IL-6.
Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice deficient in IL-6 and wild mice were immunized with antigens (myelin oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover, polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal stimulation and by antigen-primed spleen T cells in response to re-challenge with the antigen. In contrast, the induction of spleen CD4-positive T cells into Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3 plus IL-12 was not inhibited by the presence of IL-6. Thus, these results indicate that IL-6 physiologically could modulate qualitative T cell response and suggest that it augments Th(1)responses partly through its inhibitory capability of IL-4-induced Th(2)differentiation of naive T cells.
Department of Medicine III, Osaka University Medical School, 202 Yamada-oka Suita City, Osaka 565-0871, Japan. ttanak@imed3.med.osaka-u.ac.jp
T
T
Tanaka
Y
Y
Katada
S
S
Higa
H
H
Fujiwara
W
W
Wang
Y
Y
Saeki
S
S
Ohshima
Y
Y
Okuda
M
M
Suemura
T
T
Kishimoto
D000276:Adjuvants, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016853:Muromonab-CD3 / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D015850:Interleukin-6; D016853:Muromonab-CD3; D015847:Interleukin-4; D007371:Interferon-gamma