The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development


Leslie J. Berg
Department of Pathology
Rm. S3-143B
University of Massachusetts Medical School
55 Lake Avenue N
Worcester, MA 01655 USA
Tel.: +1 508 856 8371
Fax: +1 508 856 8372


Summary:  Tec family kinases are important components of antigen receptor signaling pathways in B cells, T cells, and mast cells. In T cells, three members of this family, inducible T-cell kinase (Itk), resting lymphocyte kinase (Rlk), and Tec, are expressed. In the absence of Itk and Rlk, T-cell receptor signaling is impaired, with defects in mitogen-activated protein kinase activation, Ca2+ mobilization, and actin polymerization. During T-cell development in the thymus, no role has been found for these kinases in the CD4+ versus CD8+ T-cell lineage decision; however, several studies indicate that Itk and Rlk contribute to the signaling leading to positive and negative selection. In addition, we and others have recently described an important role for Itk and Rlk in the development of conventional as opposed to innate CD4+ and CD8+ T cells. Natural killer T and γδ T-cell populations are also altered in Itk- and Rlk/Itk-deficient mice. These findings strongly suggest that the strength of T-cell receptor signaling during development determines whether T cells mature into conventional versus innate lymphocyte lineages. This lineage decision is also influenced by signaling via signaling lymphocytic activation molecule (SLAM) family receptors. Here we discuss these two signaling pathways that each contribute to conventional versus innate T-cell lineage commitment.