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However, the signals that control the maintenance and differentiation of these cells are largely unknown. Here, we demonstrated that TGF-b 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 a4 integrins (i.e., a4b1hi and a4b7lo) controlled by TGF-b. In the absence of TGF-b signaling, greatly enhanced expression of migration-related markers, including altered expression of a4 integrins led to enhanced egress of stem-like CD8+ T cells into the circulation accompanied by further differentiation into transitional states. Blocking a4 integrin significantly promoted their lymphoid tissue retention and therefore partially rescued the defective maintenance of Tcf-1+ subset in the absence of TGF-b signaling. Thus, TGF-b promotes the maintenance and inhibits the further differentiation of stem-like T cells at least partially via enforcing their lymphoid tissue residency. Overall design: Wild type and TGF-b receptor 2 conditional knockout (KO) P14 TCR transgenic CD8+ T cells were adoptively cotransferred into C57BL/6 recipients followed by LCMV Clone 13 infection. Day 15 post infection, pooled spleen and lymph node donor WT and KO P14 T cells were FACS sorted into 4 subsets based on the expression of Ly108 and CD69 (i.e., Ly108+CD69+, Ly108+CD69-, Ly108-CD69- and Ly108-CD69+). Total RNA was extracted from sorted T cells and subjected to RNA-seq analysis. Please note that one of the samples (CL_WT_1) did not pass quality control and was excluded from data processing. Thus, the *genename.txt processed data files contain total 15 data columns."],"tag":["xref:PubMed:35980385"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"TGF-b promotes stem-like T cells via enforcing their lymphoid tissue retention","description":"TGF-b promotes stem-like T cells via enforcing their lymphoid tissue retention","dates":{"last_updated":"2025-09-24","first_public":"2022-06-26"},"accession":"PRJNA851710","cross_references":{"GEO":["GSE206646"],"taxon":["10090"],"PubMed":["35980385"]}}