TCR stimulation without co-stimulatory signals induces expression of "tolerogenic" genes in memory CD4 T cells but does not compromise cell proliferation.

Published

Journal Article

Memory T cells resist co-stimulatory blockade and present a unique therapeutic challenge in transplantation and autoimmune diseases. Herein, we determined whether memory T cells express less "tolerogenic" genes than naïve T cells to reinforce a proliferative response under the deprivation of co-stimulatory signals. The expression of ∼40 tolerogenic genes in memory and naïve CD4(+) T cells was thus assessed during an in vitro TCR stimulation without co-stimulation. Briefly, upon TCR stimulation with an anti-CD3 mAb alone, memory CD4(+) T cells exhibited more proliferation than naïve CD4(+) T cells. To our surprise, at 24h upon anti-CD3 mAb stimulation, memory CD4(+) T cells expressed more than a 5-fold higher level of the transcription factor Egr2 and a 20-fold higher level of the transmembrane E3 ubiquitin ligase GRAIL than those in naïve T cells. Hence, the high-level expression of tolerogenic genes, Egr2 and GRAIL, in memory CD4(+) T cells does not prevent cell proliferation. Importantly, anti-CD3 mAb-stimulated memory CD4(+) T cells expressed high protein/gene levels of phosphorylated STAT5, Nedd4, Bcl-2, and Bcl-XL. Therefore, co-stimulation-independent proliferation of memory CD4(+) T cells may be due to elevated expression of molecules that support cell proliferation and survival, but not lack of tolerogenic molecules.

Full Text

Duke Authors

Cited Authors

  • Xie, A; Zheng, X; Khattar, M; Schroder, P; Stepkowski, S; Xia, J; Chen, W

Published Date

  • February 2015

Published In

Volume / Issue

  • 63 / 2

Start / End Page

  • 406 - 411

PubMed ID

  • 25306961

Pubmed Central ID

  • 25306961

Electronic International Standard Serial Number (EISSN)

  • 1872-9142

International Standard Serial Number (ISSN)

  • 0161-5890

Digital Object Identifier (DOI)

  • 10.1016/j.molimm.2014.09.013

Language

  • eng