CD28 blockade induces division-dependent downregulation of interleukin-2 receptor alpha
| Autor: | Linda Stempora, Mandy L. Ford, Christian P. Larsen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Interleukin 2
Immunoconjugates T-Lymphocytes T cell Immunology Population Mice Transgenic chemical and pharmacologic phenomena Biology Article Abatacept Mice CD28 Antigens Downregulation and upregulation medicine Animals Immunology and Allergy IL-2 receptor education Transplantation education.field_of_study Graft Survival Interleukin-2 Receptor alpha Subunit Antibodies Monoclonal CD28 hemic and immune systems Flow Cytometry Molecular biology Blockade medicine.anatomical_structure Gene Expression Regulation Cancer research Interleukin-2 Cell Division Signal Transduction medicine.drug |
| Zdroj: | Transplant Immunology. 24:94-99 |
| ISSN: | 0966-3274 |
| Popis: | Background Blockade of T cell costimulatory molecules represents a promising new method of attenuating donor-reactive T cell responses to promote graft survival following transplantation. However, recent studies in murine models have shown the presence of an initial high frequency of naive donor-reactive T cells may render this strategy ineffective. Methods In this report, we examined the phenotypic changes associated with CD28 blockade on T cells stimulated at increasing precursor frequencies in vitro . Results We found that treatment with the CD28 blocker CTLA-4 Ig resulted in downregulation of the alpha chain of the IL-2 receptor (CD25) in a division-dependent manner. Significantly, blockade of the CD28 pathway was more effective in down-regulating CD25 when the donor-reactive T cell population was present at low as compared to high precursor frequency. Conclusions These results imply that treatment with CD28 blockers and anti-CD25 mAbs may cooperate in promoting graft survival under conditions of low MHC matching where the donor-reactive T cell precursor frequency is high. |
| Databáze: | OpenAIRE |
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