Altered Development of CD8 + T Cell Lineages in Mice Deficient for the Tec Kinases Itk and Rlk

• Published in: Immunity (Cambridge, Mass.) Mass.), 2006-07, Vol.25 (1), p.93-104
• Main Authors: Broussard, Christine, Fleischecker, Christine, Horai, Reiko, Chetana, Madeva, Venegas, Ana M., Sharp, Leslie L., Hedrick, Stephen M., Fowlkes, B.J., Schwartzberg, Pamela L.
• Format: Article
• Language: English
• Subjects: Animals; Bone marrow; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation; Cell Lineage; CELLIMMUNO; DEVBIO; Flow cytometry; Histocompatibility Antigens - metabolism; Immune system; Kinases; Lymphocytes; Mice; Mice, Knockout; Organ Culture Techniques; Peptides; Phenotype; Protein-Tyrosine Kinases - classification; Protein-Tyrosine Kinases - deficiency; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Signal Transduction; SIGNALING; T cell receptors; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism; Time Factors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2006.05.011

Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca 2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk −/− and Rlk −/−Itk −/− mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8 + T cells in these mice do not resemble conventional CD8 + T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8 + T cell phenotypes in Itk −/− mice, arguing that altered signaling permits development of this innate-type CD8 + cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.