期刊
PLOS ONE
卷 6, 期 3, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0017423
关键词
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资金
- European Research Council (ERC)
- Ligue Nationale Contre le Cancer
- Association pour la Recherche Contre le Cancer (ARC)
- Agence Nationale de la Recherche Contre le SIDA (ANRS)
- Agence Nationale pour la Recherche (ANR)
- Association Francaise des Myopathies (AFM)
- Centre National de la Recherche Scientifique (CNRS)
- Institut Pasteur
- MRT
- ARC, France
- FCT, Portugal
We here describe novel aspects of CD8(+) and CD4(+) T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8(+) T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naive CD8(+) T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4(+) T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4(+) T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44(+)CD62L(high)) T-CM and (CD44(+)CD62L(low)) T-EM CD8(+) T cells, we found that the accumulation of TCM and TEM subsets is differentially regulated. T-CM-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4(+) T-cell help. In contrast, TEM-cell expansion was mainly determined by CD4(+) T-cell help and dependent on the expression of IL-2R beta by CD8 cells, on IL-2 produced by CD4(+) T-cells, on IL-15 and to a minor extent on IL-6.
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