Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates

Abstract

Developing thymocytes and T cells express the Tec kinases Itk, Rlk/Txk and Tec, which are critical modulators of T-cell receptor signaling, required for full activation of phospholipase Cγ, and downstream Ca(2+) and ERK-mediated signaling pathways. Over the last 10 years, data have implicated the Tec family kinases Itk and Rlk/Txk as important regulators of cytokine production by CD4(+) effector T-cell populations. Emerging data now suggest that the Tec family kinases not only influence cytokine-producing T-cell populations in the periphery, but also regulate the development of distinct innate-type cytokine-producing T-cell populations in the thymus. Together, these results suggest that the Tec family kinases play critical roles in helping shape immune responses via their effects on the differentiation and function of distinct cytokine-producing, effector T-cell populations.

Figure 1

TFKs influence cytokine production by CD4⁺ effector T cell lineages. CD4⁺ T cells differentiate into distinct cytokine producing effector lineages. Itk has been shown to affect Th2 and Th17 cytokine expression. Rlk/Txk has been proposed to promote expression of IFN-γ, a Th1 cytokine. The contribution of Tec to these lineages has only recently been appreciated.

Figure 2

Itk influences the balance of conventional and innate T cell lineages. In the absence of Itk, there is a reduction of conventional CD4⁺ and CD8⁺ cells and an expansion of innate CD4⁺ and CD8⁺ T cell lineages that rapidly produce cytokines upon activation. These innate cells contribute to immune homeostasis, responses to infection and the balance of memory-phenotype CD8⁺ cells in mice.