期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 12, 页码 3324-3338出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201546000
关键词
CD8(+) T cells; IL-2; IL-15; Memory; T-cell differentiation
类别
资金
- Canadian Institutes of Health Research [CIHR MOP-130469]
- Fonds de Recherche du Quebec - Sante
- Cole Foundation
- Canadian Child Health Clinician Scientist Program
- Institut Pasteur
- INSERM
- CIHR [MOP-89797]
- Jeanne and J.-Louis Levesque Research Chair in Immunovirology from the J.-Louis Levesque Foundation
- University of Montreal
- CHU Sainte-Justine Foundation
The ability to mount effective secondary responses is a cardinal feature of memory CD8(+) T cells. An understanding of the factors that regulate the generation and recall capacities of memory T cells remains to be ascertained. Several cues indicate that two highly related cytokines, IL-2 and IL-15, share redundant functions in this process. To establish their combined roles in memory CD8(+) T-cell development, maintenance, and secondary responses, we compared the outcome of adoptively transferred IL2R beta(+/-) or IL2R beta(-/-) CD8(+) T cells after an acute viral infection in mice. Our results demonstrate that both IL-2 and IL-15 signals condition the differentiation of primary and secondary short-lived effector cells by altering the transcriptional network governing lineage choices. These two cytokines also regulate the homeostasis of the memory T-cell pool, with effector memory CD8+ T cells being the most sensitive to these two interleukins. Noticeably, the inability to respond to both cytokines limits the proliferation and survival of primary and secondary effectors cells, whereas it does not preclude potent cytotoxic functions and viral control either initially or upon rechallenge. Globally, these results indicate that lack of IL-2 and IL-15 signaling modulates the CD8(+) T-cell differentiation program but does not impede adequate effector functions.
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