Signal integration and crosstalk during thymocyte migration and emigration

Abstract

The thymus produces self-tolerant functionally competent T cells. This occurs by the import of multipotent hematopoietic progenitors that are signalled to adopt the T cell fate. Expression of T cell specific genes, including those encoding the T cell receptor (TCR), is followed by positive and negative selection and the eventual export of mature T cells. Significant progress has been made in elucidating the signals that direct progenitor cell trafficking to, within and out of the thymus. These advances are the subject of this Review, with a particular focus on the role of reciprocal cooperative and regulatory interactions between TCR and chemokine receptor-mediated signalling.

αPIX RhoGEF Supports Positive Selection by Restraining Migration and Promoting Arrest of Thymocytes

“…After serum starvation for 20 min, cells were stimulated by TCR-crosslinking with goat F(ab9) 2 antihamster IgG (STAR104; AbD Serotec), fixed with paraformaldehyde, permeabilized with methanol, stained with anti-phospho-ERK and analyzed by FACS.…”

“…T hymocyte maturation is a dynamic process that occurs in distinct spatial compartments of the thymus with the ultimate goal of producing a T cell bearing a functional and non-self-reactive TCR (1,2). The earliest thymocyte progenitors, known as double-negative (DN) thymocytes, rearrange TCR and upregulate CD4 and CD8 coreceptors to yield CD4 + CD8 + doublepositive (DP) thymocytes.…”

The Thymic Microenvironment Differentially Regulates Development and Trafficking of Invariant NKT Cell Sublineages

“…In the context of thymocyte trafficking during T cell development and selection, the developmentally regulated expression of CX3CR1 and CXCR3 within thymic NKT sublineages clearly distinguishes them from chemokine receptor expression profiles used to define trafficking of conventional T cells within the thymus (11). To our knowledge, CX3CR1 expression within developing iNKT thymocytes has not been previously reported and, apart from one study that defines neuropilin-1 as a marker for emigrating IL-17-producing iNKT cells (9), this is the first study to identify a marker for emigration expressed within the NKT1, NKT2, and NKT17 sublineages.…”

“…In contrast, a large number of studies have highlighted the importance of lymphocyte trafficking during conventional thymocyte development. For example, guided entry of T-progenitors into the thymus, positive selection in the thymic cortex, migration of thymocytes into the thymic medulla, and seeding of the peripheral compartment all require G proteincoupled transmembrane receptors (11). Thus, thymocytes receive distinct guidance cues from the thymic microenvironment, which in turn serves to promote their development and maturation (12).…”

La protéine matricielle CYR61/CCN1 stimule la production de lymphocytes T

“…Le fonctionnement du thymus repose fortement sur le stroma thymique, un réseau conjonctif dont les principales composantes sont les cellules épithéliales thymiques (TEC). Les cellules stromales fournissent un microenvironnement propice au recrutement des cellules souches hémato-poïétiques circulant dans le sang et à leur différentiation en lymphocytes T [1,2]. Malheureusement, l'atrophie du thymus, liée à l'âge ou consécutive à des infections ou une chimiothérapie, résulte en une diminution du nombre de cellules épithéliales et donc une alté-ration de l'architecture du thymus.…”