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Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state.
- Source :
- Nature Communications; 7/6/2020, Vol. 11 Issue 1, p1-16, 16p
- Publication Year :
- 2020
-
Abstract
- CD4<superscript>+</superscript> T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether MP CD4<superscript>+</superscript> T cells are functionally heterogeneous and, if so, what signals specify the differentiation of MP cell subpopulations under homeostatic conditions is still unclear. Here we characterize MP lymphocytes as consisting of T-bet<superscript>high</superscript>, T-bet<superscript>low</superscript>, and T-bet<superscript>−</superscript> subsets, with innate, Th1-like effector activity exclusively associated with T-bet<superscript>high</superscript> cells. We further show that the latter population depends on IL-12 produced by CD8α<superscript>+</superscript> type 1 dendritic cells (DC1) for its differentiation. Finally, our data demonstrate that this tonic IL-12 production requires TLR-MyD88 signaling independent of foreign agonists, and is further enhanced by CD40-CD40L interactions between DC1 and CD4<superscript>+</superscript> T lymphocytes. We propose that optimal differentiation of T-bet<superscript>high</superscript> MP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels. CD4<superscript>+</superscript> T cells contain a T-bet<superscript>high</superscript> memory-phenotype (MP) population with innate-like functions. Here the authors characterize the requirements for their differentiation at homeostasis and identify a function for IL-12 that is tonically produced by type 1 dendritic cells in an MyD88- and CD40-dependent, but foreign PAMP-independent manner. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL differentiation
LYMPHOCYTES
HOMEOSTASIS
T cells
TECHNICAL specifications
CELLS
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 144404303
- Full Text :
- https://doi.org/10.1038/s41467-020-17136-1