한빛사논문
- 조회3,533
Abstract
Jae-Ho Cho1, Hee-Ok Kim1, Kylie Webster1, Mainthan Palendira1, Bumsuk Hahm2, Kyu-Sik Kim3, Cecile King1, Stuart Tangye1, and Jonathan Sprent1,*
1 Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;
2 Departments of Surgery and Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, MO, United States;
3 Division of Pulmonology, Chonnam National University Hwasun Hospital, Jeonnam, Korea, Republic of
* Corresponding author
Abstract
Immune responses lead to expression of immunoregulatory molecules on T cells, including 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 following exposure of naive CD8+ (but not CD4+) cells to CD3 ligation or specific peptide. Surprisingly, expression was inhibited by CD28/B7 costimulation, though not by interaction with other costimulatory molecules such as ICAM-1. 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 an NFAT-independent component of the calcineurin pathway, and CD94/NKG2A induction was markedly enhanced in the presence of calcineurin blockers such as FK506 or by 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 TGF-β) 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 expression during responses to different pathogens in vivo
논문정보
- Research article
- 2011년 05월 (BRIC 등록일 )
- 국내+국외 연구진
- 생명과학 > 면역학
댓글 작성 로그인
팝업 닫기관련 링크
