Premature Expression of Chemokine Receptor CCR9 Impairs T Cell Development
| Autor: | B. J. Fowlkes, Dalal El-Khoury, Matilde Canelles, Shoji Uehara, Paul E. Love, Sandra M. Hayes, LiQi Li |
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| Rok vydání: | 2006 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Adoptive cell transfer T-Lymphocytes T cell Transgene Blotting Western Immunology Down-Regulation CCR9 Mice Transgenic Thymus Gland Biology Mice Receptors CCR Chemokine receptor medicine Animals Humans Immunology and Allergy Receptor Microscopy Confocal Flow Cytometry Adoptive Transfer Cell biology Chemotaxis Leukocyte Thymocyte medicine.anatomical_structure Cancer research Receptors Chemokine CD8 |
| Zdroj: | The Journal of Immunology. 176:75-84 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.176.1.75 |
| Popis: | During thymocyte development, CCR9 is expressed on late CD4−CD8− (double-negative (DN)) and CD4+CD8+ (double-positive) cells, but is subsequently down-regulated as cells transition to the mature CD4+ or CD8+ (single-positive (SP)) stage. This pattern of expression has led to speculation that CCR9 may regulate thymocyte trafficking and/or export. In this study, we generated transgenic mice in which CCR9 surface expression was maintained throughout T cell development. Significantly, forced expression of CCR9 on mature SP thymocytes did not inhibit their export from the thymus, indicating that CCR9 down-regulation is not essential for thymocyte emigration. CCR9 was also expressed prematurely on immature DN thymocytes in CCR9 transgenic mice. Early expression of CCR9 resulted in a partial block of development at the DN stage and a marked reduction in the numbers of double-positive and SP thymocytes. Moreover, in CCR9-transgenic mice, CD25high DN cells were scattered throughout the cortex rather than confined to the subcapsular region of the thymus. Together, these results suggest that regulated expression of CCR9 is critical for normal development of immature thymocytes, but that down-regulation of CCR9 is not a prerequisite for thymocyte emigration. |
| Databáze: | OpenAIRE |
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