title: The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells.
abstract: The Tec family tyrosine kinases, Itk and Rlk, are expressed in thymocytes and peripheral T cells and regulate thresholds of T cell receptor signaling. Yet little is known about the specific role of Itk- and Rlk-dependent signals in CD8(+) T cell maturation. We show here that Itk(-/-) and Rlk(-/-)Itk(-/-) mice were nearly devoid of conventional CD8(+) T cells and, instead, contained a large population of CD8(+) T cells that bear striking similarity to lineages of innate lymphocytes. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes and T cells were CD44(hi), CD122(+), and NK1.1(+); were able to produce interferon-gamma directly ex vivo; and were dependent on interleukin-15. Itk(-/-) and Rlk(-/-)Itk(-/-) CD8(+) thymocytes expressed abundant transcripts for the T box transcription factor, eomesodermin, correlating with their phenotype and function. These data indicate a critical role for Itk and Rlk in conventional CD8(+) T cell development in the thymus.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA.
authors.forename: Luana O
authors.initials: LO
authors.lastname: Atherly
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lucas
authors.forename: Martin
authors.initials: M
authors.lastname: Felices
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Yin
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Berg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: C103223:EOMES protein, Xenopus; D018960:Hyaluronan Receptors; D019409:Interleukin-15; D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins; D029867:Xenopus Proteins; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase