Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP
| Autor: | Geoffry Knudsen, Qi Jiang, Hua Su, Lishan Su, Whitney S. Helms |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
medicine.medical_specialty Stromal cell CD8 Antigens Immunology Population chemical and pharmacologic phenomena Thymus Gland Biology Organ culture T-Lymphocytes Regulatory 03 medical and health sciences Paracrine signalling Mice 0302 clinical medicine Organ Culture Techniques Thymic Stromal Lymphopoietin Internal medicine TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY medicine Animals education Cells Cultured 030304 developmental biology 0303 health sciences education.field_of_study FOXP3 Forkhead Transcription Factors Receptors Interleukin-2 hemic and immune systems Embryonic stem cell Cell biology Thymocyte Endocrinology Animals Newborn Cytokines lcsh:RC581-607 CD8 030215 immunology Research Article |
| Zdroj: | BMC Immunology, Vol 7, Iss 1, p 6 (2006) BMC Immunology |
| ISSN: | 1471-2172 |
| Popis: | BackgroundGeneration of functional CD4+CD8-CD25+regulatory T cells (Treg) in the murine thymus depends on FoxP3. Removal of the thymus from neonatal mice has been shown to result in a multiple organ autoimmune disease phenotype that can be prevented by introducing the FoxP3+Treg population to the animal. It has therefore, been proposed that functional FoxP3+Treg cells are not made in the neonatal thymus; however, it remains unclear when and where functional FoxP3+CD4+CD8-CD25+thymocytes are generated in postnatal thymus.ResultsWe report that neither FoxP3 mRNA nor protein is expressed in CD4+CD8-CD25+, or CD4+CD8-CD25-thymocytes until 3–4 days post birth, despite the presence of mature CD4+CD8-CD25+/-thymocytes in the thymus by 1–2 days after birth. FoxP3-CD4+CD8-CD25+thymocytes from day 2 newborn mice show no Treg activity. Interestingly, we are able to detect low numbers of FoxP3+thymocytes dispersed throughout the medullary region of the thymus as early as 3–4 days post birth. Expression of FoxP3 is induced in embryonic day 17 fetal thymus organ culture (FTOC) after 4–6 days of in vitro culture. Treatment of FTOCs with thymic stromal derived lymphopoietin (TSLP) enhanced expression of FoxP3, and blocking the TSLP receptor reduces FoxP3 expression in FTOC. Furthermore, TSLP stimulates FoxP3 expression in purified CD4+CD8-thymocytes, but not in CD4+CD8+, CD4-CD8+and CD4-CD8-thymocytes.ConclusionExpression of FoxP3 or Treg maturation is ontogenically distinct and kinetically delayed from the generation of CD4+CD8-CD25+or CD4+CD8-CD25-thymocytes in the postnatal thymus. TSLP produced from medullary thymic epithelia cells (mTEC) contributes to the expression of FoxP3 and the maturation of natural regulatory T cells. Overall, these results suggest that the development of Treg cells requires paracrine signaling during late stages of thymocyte maturation that is distinct from signaling during positive or negative selection. |
| Databáze: | OpenAIRE |
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