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EBAG9 controls CD8(+) T cell memory formation responding to tumor challenge in mice

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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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