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Memory CD8 T cells are vulnerable to chronic IFN-γ signals but not to CD4 T cell deficiency in MHCII-deficient mice.
- Source :
- Nature Communications; 5/28/2024, Vol. 15 Issue 1, p1-15, 15p
- Publication Year :
- 2024
-
Abstract
- The mechanisms by which the number of memory CD8 T cells is stably maintained remains incompletely understood. It has been postulated that maintaining them requires help from CD4 T cells, because adoptively transferred memory CD8 T cells persist poorly in MHC class II (MHCII)-deficient mice. Here we show that chronic interferon-γ signals, not CD4 T cell-deficiency, are responsible for their attrition in MHCII-deficient environments. Excess IFN-γ is produced primarily by endogenous colonic CD8 T cells in MHCII-deficient mice. IFN-γ neutralization restores the number of memory CD8 T cells in MHCII-deficient mice, whereas repeated IFN-γ administration or transduction of a gain-of-function STAT1 mutant reduces their number in wild-type mice. CD127<superscript>high</superscript> memory cells proliferate actively in response to IFN-γ signals, but are more susceptible to attrition than CD127<superscript>low</superscript> terminally differentiated effector memory cells. Furthermore, single-cell RNA-sequencing of memory CD8 T cells reveals proliferating cells that resemble short-lived, terminal effector cells and documents global downregulation of gene signatures of long-lived memory cells in MHCII-deficient environments. We propose that chronic IFN-γ signals deplete memory CD8 T cells by compromising their long-term survival and by diverting self-renewing CD127<superscript>high</superscript> cells toward terminal differentiation. Memory CD8<superscript>+</superscript> T cells persist poorly in MHCII-deficient mice. Here the authors show that this CD8<superscript>+</superscript> T cell attrition is not caused by a lack of CD4<superscript>+</superscript> T cell help, as previously proposed, but by chronic IFN-γ signals derived from endogenous colonic CD8<superscript>+</superscript> T cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMMUNOLOGIC memory
T cells
CD4 antigen
INTERFERON receptors
MICE
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 15
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 177540065
- Full Text :
- https://doi.org/10.1038/s41467-024-48704-4