TECK: A Novel CC Chemokine Specifically Expressed by Thymic Dendritic Cells and Potentially Involved in T Cell Development

The present study was performed to identify cells responsible for the elimination of T cells reactive with minor lymphocyte-stimulating (Mls) antigens during T cell development. Experiments were carried out in a fetal thymus organ culture (FTOC) system. To examine the tolerance-inducing activity, various populations of cells from adult CBA/J (Mls-1a) mice were injected into deoxyguanosine (dGuo)-treated FTOC of C3H/He (Mls-1b) mice with a microinjector, and 2 d later, the thymus lobes were injected with fetal thymus cells from C3H/He mice as T cell precursors. After 14 d of cultivation, cells were harvested and assayed for the expression of the T cell receptor V beta 6 element. The absence or marked reduction of T cells expressing V beta 6 at high levels (V beta 6high) was regarded as indicating the deletion of Mls-1a-reactive T cells. T cell-depleted populations of thymic as well as splenic cells from CBA/J mice were able to induce clonal deletion. Further characterization of the effector cells was carried out by fractionating the spleen cells before injecting them into dGuo-FTOC. None of the dish-adherent population, dish-nonadherent population, or purified B cells alone were able to induce clonal deletion, whereas the addition of purified B cells to adherent cells restored tolerance inducibility. It was further shown that a combination of CBA/J B cells and C3H/He dendritic cells was effective in eliminating Mls-reactive clones. These results indicate that for the deletion of clones reactive with Mls antigens during T cell development in the thymus, both DC and B cells are required.

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Decreased expression of indoleamine 2,3-dioxygenase 1 in dendritic cells contributes to impaired regulatory T cell development in immune thrombocytopenia

Annals of Hematology ◽

10.1007/s00277-012-1556-5 ◽

2012 ◽

Vol 92 (1) ◽

pp. 67-78 ◽

Cited By ~ 29

Author(s):

Lucia Catani ◽

Daria Sollazzo ◽

Sara Trabanelli ◽

Antonio Curti ◽

Cecilia Evangelisti ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Regulatory T Cell ◽

Immune Thrombocytopenia ◽

T Cell Development ◽

Cell Development ◽

Indoleamine 2,3 Dioxygenase

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Faculty Opinions recommendation of Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8487956.8958055 ◽

2011 ◽

Author(s):

Stephen Cobbold

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Regulatory T Cell ◽

T Cell Development ◽

Cell Development

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Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes

Blood ◽

10.1182/blood.v98.9.2626 ◽

2001 ◽

Vol 98 (9) ◽

pp. 2626-2632 ◽

Cited By ~ 221

Author(s):

Marc-André Wurbel ◽

Marie Malissen ◽

Delphine Guy-Grand ◽

Eric Meffre ◽

Michel C. Nussenzweig ◽

...

Keyword(s):

Small Intestine ◽

T Cell ◽

B Cells ◽

T Cell Receptor ◽

Chemokine Receptor ◽

T Cell Development ◽

Cell Receptor ◽

Cell Development ◽

Detectable Effect ◽

Cc Chemokine

Abstract CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in double- and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development. It was noted that there was only a one-day lag in the appearance of double-positive cells during fetal ontogeny in CCR9−/− thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9−/− mice failed to respond to TECK/CCL25. Taken together, these results suggest that in thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25, and that it is dispensable for proper T-cell development. Bone marrow pre-pro–B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pre-pro–B cells in CCR9−/−mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell–to–epithelial cell ratio is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor γδ+ compartment.

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