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

Rehm, A.; Wirges, A.; Hoser, D.; Fischer, C.; Herda, S.; Gerlach, K.; Sauer, S.; Willimsky, G.; Hoepken, U.E.

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., Wirges, A., Hoser, D., Fischer, C., Herda, S., Gerlach, K., Sauer, S., 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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