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CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

Abstract：

:Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimulate the proliferation of B6 anti-bm12 CD4+ T cells. While stimulation in vitro to B6 splenic T cells with bm12 antigen-presenting cells (APC) induced IL-2 mRNA expression and IL-2 production, T cells stimulated with bm12 B cells expressed much less IL-2 mRNA and secreted very low but detectable levels of IL-2. Moreover, the T cells stimulated with the bm12 B cells did not proliferate and this was not corrected by the addition of rIL-2 responsiveness. Further, whereas IL-2 receptor (IL-2R) alpha chain expression was significantly induced on B6 T cells stimulated with bm12 APC; stimulation with bm12 B cells did not induce IL-2R expression over background levels. However, virgin T cells stimulated with both bm12 B cells and anti-CD28 mAb proliferated and displayed a dramatic increase in IL-2 production as well as IL-2R expression to levels commensurate with those resulting from bm12 B cells plus anti-CD28 mAb even in the presence of sufficient amounts of anti-IL-2 mAb for neutralizing produced IL-2; while levels of IL-2R were significantly lower compared to those induced in the absence of anti-IL-2 mAb, increased frequencies of IL-2R+ cells were comparable. Conversely, IL-2R was not induced by bm12 B cell stimulation in the presence of IL-2. Moreover, IL-2R expression and proliferation induced by stimulation with bm12 APC was inhibited by CTLA-4-Ig, a soluble recombinant fusion protein capable of blocking the CD28 co-stimulatory signals not only stimulate IL-2 production but also induce IL-2R expression by an IL-2-independent mechanism.

journal_name

Int Immunol

journal_title

International immunology

authors

Toyooka K,Maruo S,Iwahori T,Yamamoto N,Tai XG,Abe R,Takahama Y,Murakami M,Uede T,Hamaoka T,Fujiwara H

doi

10.1093/intimm/8.2.159

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

159-69

issue

eissn

0953-8178

issn

1460-2377

journal_volume

pub_type

杂志文章

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CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.