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| Item Type: | Article |
|---|---|
| Title: | EBAG9 controls CD8(+) T cell memory formation responding to tumor challenge in mice |
| Creators Name: | Rehm, A. and Wirges, A. and Hoser, D. and Fischer, C. and Herda, S. and Gerlach, K. and Sauer, S. and Willimsky, G. and Hoepken, U.E. |
| Abstract: | Insight into processes that determine CD8(+) T cell memory formation has been obtained from infection models. These models are biased toward an inflammatory milieu and often employ high avidity CD8(+) T cells in adoptive transfer procedures. It is unclear whether these conditions mimic the differentiation processes of an endogenous repertoire that proceed upon non-inflammatory conditions prevailing in premalignant tumor lesions. We examined the role of cytolytic capacity on CD8(+) T cell fate decisions when primed by tumor cells or by minor histocompatibility antigen-mismatched leukocytes. CD8(+) memory commitment was analyzed in Ebag9-deficient mice that exhibit an enhanced tumor cell lysis. This property endowed Ebag9(-/-) mice with extended control of Tcl-1 oncogene-induced chronic lymphocytic leukemia progression. In Ebag9(-/-) mice, an expanded memory population was obtained for anti-HY and anti-SV40 T antigen-specific T cells, despite unchanged effector frequencies in the primary response. By comparing the single-cell transcriptomes of CD8(+) T cells responding to tumor cell vaccination, we found differential distribution of subpopulations between Ebag9(+/+) and Ebag9(-/-) T cells. In Ebag9(-/-) cells, these larger clusters contained genes encoding transcription factors regulating memory cell differentiation, along with anti-apoptotic gene functions. Our findings link EBAG9-controlled cytolytic activity and the commitment to the CD8(+) memory lineage. |
| Keywords: | Adoptive Transfer, CD8-Positive T-Lymphocytes, Minor Histocompatibility Antigens, Neoplasms, Animals, Mice |
| Source: | JCI Insight |
| ISSN: | 2379-3708 |
| Publisher: | American Society for Clinical Investigation |
| Volume: | 7 |
| Number: | 11 |
| Page Range: | e155534 |
| Date: | 8 June 2022 |
| Official Publication: | https://doi.org/10.1172/jci.insight.155534 |
| PubMed: | View item in PubMed |
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