TY - JOUR
T1 - Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8+ tissue-resident memory T cells
AU - Peng, Changwei
AU - Huggins, Matthew A.
AU - Wanhainen, Kelsey M.
AU - Knutson, Todd P.
AU - Lu, Hanbin
AU - Georgiev, Hristo
AU - Mittelsteadt, Kristen L.
AU - Jarjour, Nicholas N.
AU - Wang, Haiguang
AU - Hogquist, Kristin A.
AU - Campbell, Daniel J.
AU - Borges da Silva, Henrique
AU - Jameson, Stephen C.
N1 - Funding Information:
We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. ( R01 AI038903 and AI145147 ). The graphical abstract was created with BioRender.com.
Funding Information:
We thank the members of the Jamequist lab for intellectual input. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported. This work was funded by NIH awards to S.C.J. (R01 AI038903 and AI145147). The graphical abstract was created with BioRender.com. C.P. and S.C.J. conceived the project and designed the experiments. D.J.C. K.A.H. and S.C.J. provided mice and reagents for all experiments. C.P. M.A.H. K.M.W. H.G. K.L.M. N.N.J. H.W. and H.B.d.S. performed the experiments. C.P. H.L. T.P.K. and S.C.J. analyzed the data. C.P. and S.C.J. wrote the manuscript, with input from all authors. The authors declare no competing interests.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8+ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos−/− CD8+ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8+ Trm cells but not their maintenance. ICOS ligation during CD8+ T cell priming did not determine Trm induction; rather, effector CD8+ T cells showed reduced Trm differentiation after seeding into Icosl−/− mice. IcosYF/YF CD8+ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos−/− Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8+ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.
AB - Elevated gene expression of the costimulatory receptor Icos is a hallmark of CD8+ tissue-resident memory (Trm) T cells. Here, we examined the contribution of ICOS in Trm cell differentiation. Upon transfer into WT mice, Icos−/− CD8+ T cells exhibited defective Trm generation but produced recirculating memory populations normally. ICOS deficiency or ICOS-L blockade compromised establishment of CD8+ Trm cells but not their maintenance. ICOS ligation during CD8+ T cell priming did not determine Trm induction; rather, effector CD8+ T cells showed reduced Trm differentiation after seeding into Icosl−/− mice. IcosYF/YF CD8+ T cells were compromised in Trm generation, indicating a critical role for PI3K signaling. Modest transcriptional changes in the few Icos−/− Trm cells suggest that ICOS-PI3K signaling primarily enhances the efficiency of CD8+ T cell tissue residency. Thus, local ICOS signaling promotes production of Trm cells, providing insight into the contribution of costimulatory signals in the generation of tissue-resident populations.
KW - ICOS
KW - PI3K
KW - resident memory T cells
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U2 - 10.1016/j.immuni.2021.11.017
DO - 10.1016/j.immuni.2021.11.017
M3 - Article
C2 - 34932944
AN - SCOPUS:85122271938
SN - 1074-7613
VL - 55
SP - 98-114.e5
JO - Immunity
JF - Immunity
IS - 1
ER -