Engagement of the costimulatory molecule ICOS in tissues promotes establishment of CD8 + tissue-resident memory T cells.

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. Icos ^YF/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.
Competing Interests: Declaration of interests The authors declare no competing interests.
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