Intracellular Signals of T Cell Costimulation

Song, Jianxun; Lei, Fengyang; Xiong, Xiaofang; Haque, Rizwanul

doi:10.1038/cmi.2008.30

Cited by 57 publications

(55 citation statements)

References 87 publications

(101 reference statements)

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“…As a result there is a hastened entry of activated T cells into the cell cycle in cultures with RBC in comparison with cultures without, namely at days 2 and 3 after activation, and our results point to the PI3K/Akt axis as a putative target of the RBC bioactivities. Akt is thought to be an upstream regulator of NF-kB, reinforcing the possible involvement of this transcription factor on the RBC effect [32].…”

Section: Discussionmentioning

confidence: 99%

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Antunes

Brandão²,

Carvalho³

et al. 2009

Cell. Mol. Life Sci.

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Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli,including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.

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Section: Discussionmentioning

confidence: 99%

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Antunes

Brandão²,

Carvalho³

et al. 2009

Cell. Mol. Life Sci.

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“…Whereas costimulatory signals that promote T-cell activation and cell survival are closely linked (29), the intracellular molecules that transmit these signals can be distinct (30,31). That the defect in cell survival occurs following further activation suggests that the stress induced by T-cell activation initiates apoptosis in the memory cells.…”

Section: Discussionmentioning

confidence: 99%

Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation

David

Crawford

Garside³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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A major goal for immunotherapy is to tolerize the immune cells that coordinate tissue damage in autoimmune and alloantigen responses. CD4 T cells play a central role in many of these conditions and improved antigen-specific regulation or removal of these cells could revolutionize current treatments. A confounding factor is that little is known about whether and how tolerance is induced in memory CD4 T cells. We used MHC class II tetramers to track and analyze a population of endogenous antigen-specific memory CD4 T cells exposed to soluble peptide in the absence of adjuvant. We found that such memory T cells proliferated and reentered the memory pool apparently unperturbed by the incomplete activation signals provided by the peptide. Upon further restimulation in vivo, CD4 memory T cells that had been previously exposed to peptide proliferated, provided help to primary responding B cells, and migrated to inflamed sites. However, these reactivated memory cells failed to survive. The reduction in T-cell number was marked by low expression of the antiapoptotic molecule B cell lymphoma 2 (Bcl2) and increased expression of activated caspase molecules. Consequently, these cells failed to sustain a delayed-type hypersensitivity response. Moreover, following two separate exposures to soluble antigen, no T-cell recall response and no helper activity for B cells could be detected. These results suggest that the induction of tolerance in memory CD4 T cells is possible but that deletion and permanent removal of the antigen-specific T cells requires reactivation following exposure to the tolerogenic antigen.

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“…Several of these targets were of potential interest because of their known role in the control of T-cell survival, proliferation, and differentiation as well as neoplastic transformation, including NOTCH3, 32 BCL2L1, 33 CDKN2D, 34 and NFKB1. 35 …”

Section: Org Frommentioning

confidence: 99%

Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150

Ghisi

Corradin

Basso

et al. 2011

Blood

202

181

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Intracellular Signals of T Cell Costimulation

Abstract: Ligation of T cell receptor (TCR

Cited by 57 publications

References 87 publications

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation

Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150

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