CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells
| Autor: | Antal Rot, Martin A. Schneider, Martin Lipp, Moore Henrietta, Josef G. Meingassner |
|---|---|
| Přispěvatelé: | MDC Library |
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Dermatitis Contact T-Lymphocytes Regulatory Mice Interleukin 21 immune system diseases Immunology and Allergy Cytotoxic T cell IL-2 receptor Mice Knockout CD28 FOXP3 Forkhead Transcription Factors hemic and immune systems Articles Natural killer T cell CCR2 Receptors Cell biology CD44 Antigens Hyaluronan Receptors medicine.anatomical_structure Chemokine Receptors Receptors Chemokine Integrin alpha Chains tissues Receptors CCR7 Regulatory T-Lymphocytes Receptors CCR2 T cell Immunology Receptors Antigen T-Cell 570 Life Sciences chemical and pharmacologic phenomena Biology Article 610 Medical Sciences Medicine Contact Dermatitis Antigens CD medicine Animals Antigen-presenting cell Cell Proliferation CCR7 Receptors Interleukin-2 Receptor alpha Subunit Gene Expression Regulation Lymph Nodes T-Cell Antigen Receptors Spleen |
| Zdroj: | Journal of Experimental Medicine 204 (4): 735-745. The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3+ CD4+ CD25+ regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3+ T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel disease. |
| Databáze: | OpenAIRE |
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