Differential production of IL-12 in BALB/c and DBA/2 mice controls IL-4 versus IFN-gamma synthesis in primed CD4 lymphocytes

被引:36
作者
Gieni, RS
Fang, Y
Trinchieri, G
Umetsu, DT
DeKruyff, RH
机构
[1] STANFORD UNIV,DEPT PEDIAT,DIV IMMUNOL & TRANSPLANTAT BIOL,STANFORD,CA 94305
[2] WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104
关键词
antigen-presenting cell; cytokine synthesis; IFN-gamma; IL-4; IL-12;
D O I
10.1093/intimm/8.10.1511
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The profile of cytokines produced by CD4 T cells is profoundly influenced by the presence of IL-12, Here we demonstrate that during re-stimulation of antigen-specific immune responses in vitro, antigen-primed lymph node cells from DBA/2 mice produced 3- to 30-fold more IL-12 than did cells from BALB/c mice, which are identical at the major histocompatibility locus, The strain differences in IL-12 production were observed only in antigen-driven responses (and not in responses induced by bacterial products), and were dependent upon an interaction between CD4 T cells and lymph node adherent cells, In addition, differences in the quantity of IL-12 produced by DBA/2 and BALB/c antigen-presenting cells (APC) was not dependent on differential production of IFN-gamma by T cells, since APC from DBA/2 mice still produced much greater quantities of IL-12 than did BALB/c APC when each was cultured with the same H-2(d)-restricted T(h)2 clones, in the complete absence of IFN-gamma, or when each was cultured with primed (BALB/c x DBA/2)F-1 T cells. The level of IL-12 produced in the cultures critically affected cytokine production in CD4 T cells, since neutralization of endogenous IL-12 in DBA/2 cultures, which are predisposed towards developing T(h)1 responses, reduced IFN-gamma production and enhanced IL-4 synthesis to levels normally seen in BALB/c cultures, which are predisposed toward developing Th2 responses, We propose therefore that differential production of antigen-driven IL-12 is a mechanism by which the genetic background in DBA/2 and BALB/c mice can affect the pattern of cytokine synthesis by T cells during the development of adaptive immune responses.
引用
收藏
页码:1511 / 1520
页数:10
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