SAP protein-dependent natural killer T-like cells regulate the development of CD8(+) T cells with innate lymphocyte characteristics.
CD8(+) T cells are selected via low-affinity interaction with MHC class I molecules on thymic epithelial cells (TECs). However, compromised T cell receptor signaling was proposed to force CD8(+) T cell selection on hematopoietic cells through a SLAM-associated protein (SAP)-dependent mechanism similar to NKT cells. The outcome is an unconventional CD8(+) T cell with phenotypic and functional characteristics of innate lymphocytes. Here we showed that Id3(-/-) CD8(+) T cells had an innate-like phenotype and required SAP for their development. However, like conventional CD8(+) T cells, Id3(-/-) CD8(+) thymocytes were selected on TECs. The requirement for SAP and the innate-like phenotype was not intrinsic to Id3(-/-) CD8(+) thymocytes. Rather, an expanded population of NKT-like cells induced the innate phenotype on CD8(+) T cells through production of interleukin-4. Our findings reveal that accumulation of NKT-like cells promotes conventional CD8(+) thymocytes to acquire innate lymphocyte characteristics.
Verykokakis
Mihalis
M
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Boos
Markus D
MD
Bendelac
Albert
A
Kee
Barbara L
BL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007113:Immunity, Innate; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D010641:Phenotype; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D051796:Inhibitor of Differentiation Proteins; D047908:Intracellular Signaling Peptides and Proteins; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C067679:Idb3 protein, mouse; D015847:Interleukin-4