期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 10, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20211538
关键词
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资金
- National Institutes of Health [AI125701, AI139721]
- Cancer Research Institute CLIP program
- American Cancer Society [RSG-18-222-01-LIB]
- University of Texas Health Science Center at San Antonio
- Mays Cancer Center National Institutes of Health/National Cancer Institute grant [P30 CA054174]
- National Center for Advancing Translational Science, National Institutes of Health [UL1 TR002645]
This study reveals that TGF-beta promotes lymphoid residency and partially inhibits the effector differentiation of stem-like T cells through controlling the expression of alpha 4 integrins.
Stem-like CD8(+) T cells sustain the antigen-specific CD8(+) T cell response during chronic antigen exposure. However, the signals that control the maintenance and differentiation of these cells are largely unknown. Here, we demonstrated that TGF-beta was essential for the optimal maintenance of these cells and inhibited their differentiation into migratory effectors during chronic viral infection. Mechanistically, stem-like CD8(+) T cells carried a unique expression pattern of alpha 4 integrins (i.e., alpha 4 beta 1(hi) and alpha 4 beta 7(lo)) controlled by TGF-beta. In the absence of TGF-beta signaling, greatly enhanced expression of migration-related markers, including altered expression of alpha 4 integrins, led to enhanced egress of stem-like CD8(+) T cells into circulation accompanied by further differentiation into transitional states. Blocking alpha 4 integrin significantly promoted their lymphoid tissue retention and therefore partially rescued the defective maintenance of Tcf-1(+) subset in the absence of TGF-beta signaling. Thus, TGF-beta promotes the maintenance and inhibits the further differentiation of stem-like T cells at least partially via enforcing their lymphoid tissue residency. The signals that control the differentiation of Tcf-1(+) CD8(+) T cells are not entirely known. Here, the authors find that TGF-beta promotes lymphoid residency and inhibits the effector differentiation of Tcf-1(+) T cells partially via controlling the expression of alpha 4 integrins.
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