Calcineurin-dependent negative regulation of CD94/NKG2A expression on naive CD8(+) T cells
SCIE
SCOPUS
- Title
- Calcineurin-dependent negative regulation of CD94/NKG2A expression on naive CD8(+) T cells
- Authors
- JAE-HO CHO; HEE-OK KIM; KYLIE WEBSTER; MAINTHAN PALENDIRA; BUMSUK HAHM; KYU-SIK KIM; CECILE KING; STUART TANGYE; Sprent, J
- Date Issued
- 2011-07-07
- Publisher
- American Society of Hematology
- Abstract
- Immune responses lead to expression of immunoregulatory molecules on T cells, including natural killer (NK) receptors, such as CD94/NKG2A on CD8(+) T cells; these receptors restrain CD8(+) responses, thereby preventing T-cell exhaustion in chronic infections and limiting immunopathology. Here, we examined the requirements for inducing CD94/NKG2A on T cells responding to antigen. In vitro, moderate induction of CD94/NKG2A expression occurred after exposure of naive CD8(+) (but not CD4(+)) cells to CD3 ligation or specific peptide. Surprisingly, expression was inhibited by CD28/B7 costimulation. Such inhibition applied only to CD94/NKG2A and not other NK receptors (NKG2D) and was mediated by IL-2. Inhibition by IL-2 occurred via a NFAT cell-independent component of the calcineurin pathway, and CD94/NKG2A induction was markedly enhanced in the presence of calcineurin blockers, such as FK506 or using calcineurin-deficient T cells, both in vitro and in vivo. In addition to CD28-dependent inhibition by IL-2, CD94/NKG2A expression was impaired by several other cytokines (IL-4, IL-23, and transforming growth factor-beta) but enhanced by others (IL-6, IL-10, and IL-21). The complex interplay between these various stimuli may account for the variable expression of CD94/NKG2A during responses to different pathogens in vivo. (Blood. 2011;118(1):116-128)
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/92458
- DOI
- 10.1182/BLOOD-2010-11-317396
- ISSN
- 0006-4971
- Article Type
- Article
- Citation
- BLOOD, vol. 1, no. 1, page. 116 - 128, 2011-07-07
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