ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/048/SRR19779748/SRR19779748_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/040/SRR19779740/SRR19779740_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/041/SRR19779741/SRR19779741_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/035/SRR19779735/SRR19779735_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/047/SRR19779747/SRR19779747_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/045/SRR19779745/SRR19779745_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/044/SRR19779744/SRR19779744_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/042/SRR19779742/SRR19779742_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/036/SRR19779736/SRR19779736_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/037/SRR19779737/SRR19779737_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/038/SRR19779738/SRR19779738_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/049/SRR19779749/SRR19779749_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/043/SRR19779743/SRR19779743_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/044/SRR19779744/SRR19779744_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/035/SRR19779735/SRR19779735_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/043/SRR19779743/SRR19779743_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/047/SRR19779747/SRR19779747_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/046/SRR19779746/SRR19779746_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/039/SRR19779739/SRR19779739_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/041/SRR19779741/SRR19779741_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/034/SRR19779734/SRR19779734_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/038/SRR19779738/SRR19779738_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/048/SRR19779748/SRR19779748_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/040/SRR19779740/SRR19779740_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/042/SRR19779742/SRR19779742_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/049/SRR19779749/SRR19779749_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/046/SRR19779746/SRR19779746_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/045/SRR19779745/SRR19779745_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/039/SRR19779739/SRR19779739_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/036/SRR19779736/SRR19779736_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/037/SRR19779737/SRR19779737_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR197/034/SRR19779734/SRR19779734_2.fastq.gzprimaryOK200GenomicsUTHSAhttps://www.ebi.ac.uk/ena/browser/view/PRJNA851710Mus musculusStem-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-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.xref:PubMed:35980385ENAfalseTGF-b promotes stem-like T cells via enforcing their lymphoid tissue retentionTGF-b promotes stem-like T cells via enforcing their lymphoid tissue retention2025-09-242022-06-26PRJNA851710GSE2066461009035980385