Requirements for selection of conventional and innate T lymphocyte lineages.
Mice deficient in the Tec kinase Itk develop a large population of CD8(+) T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8(+) T cells can be selected on hematopoietic cells. We demonstrate that these CD8(+) T cell phenotypes resulted from selection on hematopoietic cells-forcing selection on the thymic stroma reduced the number and innate phenotypes of mature Itk-deficient CD8(+) T cells. We further show that, similar to NKT cells, selection of innate-type CD8(+) T cells in Itk(-/-) mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8(+) T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells.
Horai
Reiko
R
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mueller
Kristen L
KL
Handon
Robin A
RA
Cannons
Jennifer L
JL
Anderson
Stacie M
SM
Kirby
Martha R
MR
Schwartzberg
Pamela L
PL
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D005434:Flow Cytometry; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D018106:CD28 Antigens; D047908:Intracellular Signaling Peptides and Proteins; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C064626:Ltk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases