TY - JOUR
T1 - TGF-β promotes stem-like T cells via enforcing their lymphoid tissue retention
AU - Ma, Chaoyu
AU - Wang, Liwen
AU - Liao, Wei
AU - Liu, Yong
AU - Mishra, Shruti
AU - Li, Guo
AU - Zhang, Xin
AU - Qiu, Yuanzheng
AU - Lu, Qianjin
AU - Zhang, Nu
N1 - Publisher Copyright:
© 2022 Ma et al.
PY - 2022/10/3
Y1 - 2022/10/3
N2 - 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-β 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 α4 integrins (i.e., α4β1hi and α4β7lo) controlled by TGF-β. In the absence of TGF-β signaling, greatly enhanced expression of migration-related markers, including altered expression of α4 integrins, led to enhanced egress of stem-like CD8+ T cells into circulation accompanied by further differentiation into transitional states. Blocking α4 integrin significantly promoted their lymphoid tissue retention and therefore partially rescued the defective maintenance of Tcf-1+ subset in the absence of TGF-β signaling. Thus, TGF-β promotes the maintenance and inhibits the further differentiation of stem-like T cells at least partially via enforcing their lymphoid tissue residency.
AB - 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-β 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 α4 integrins (i.e., α4β1hi and α4β7lo) controlled by TGF-β. In the absence of TGF-β signaling, greatly enhanced expression of migration-related markers, including altered expression of α4 integrins, led to enhanced egress of stem-like CD8+ T cells into circulation accompanied by further differentiation into transitional states. Blocking α4 integrin significantly promoted their lymphoid tissue retention and therefore partially rescued the defective maintenance of Tcf-1+ subset in the absence of TGF-β signaling. Thus, TGF-β promotes the maintenance and inhibits the further differentiation of stem-like T cells at least partially via enforcing their lymphoid tissue residency.
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U2 - 10.1084/jem.20211538
DO - 10.1084/jem.20211538
M3 - Article
C2 - 35980385
AN - SCOPUS:85136910707
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
M1 - e20211538
ER -