2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses
| Autor: | Lumelle A. Schneeweis, Steven G. Nadler, Danya Liu, Dawn K. Stetsko, Scott M. Krummey, Maylene E. Wagener, I. Raul Badell, Mandy L. Ford, Suzanne J. Suchard |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunoconjugates T cell Immunology Cell Mice Transgenic chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Biology Lymphocyte Activation B7-H1 Antigen Article Abatacept Inducible T-Cell Co-Stimulator Protein Mice CD28 Antigens Antigens CD Signaling Lymphocytic Activation Molecule Family medicine Animals Immunology and Allergy Cytotoxic T cell CTLA-4 Antigen Receptors Immunologic Receptor Mice Knockout Mice Inbred BALB C Graft Survival Models Immunological Antibodies Monoclonal CD28 hemic and immune systems Skin Transplantation Allografts Molecular biology Up-Regulation 3. Good health Blockade Cell biology Mice Inbred C57BL medicine.anatomical_structure Signal transduction CD8 Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20130902 |
| Popis: | Blockade of CD28 signals results in the up-regulation of 2B4 on primary CD8+ effectors and plays a critical role in controlling antigen-specific CD8+ T cell responses. Mounting evidence in models of both autoimmunity and chronic viral infection suggests that the outcome of T cell activation is critically impacted by the constellation of co-stimulatory and co-inhibitory receptors expressed on the cell surface. Here, we identified a critical role for the co-inhibitory SLAM family member 2B4 (CD244) in attenuating primary antigen-specific CD8+ T cell responses in the presence of immune modulation with selective CD28 blockade. Our results reveal a specific up-regulation of 2B4 on antigen-specific CD8+ T cells in animals in which CD28 signaling was blocked. However, 2B4 up-regulation was not observed in animals treated with CTLA-4 Ig (abatacept) or CD28 blockade in the presence of anti–CTLA-4 mAb. 2B4 up-regulation after CD28 blockade was functionally significant, as the inhibitory impact of CD28 blockade was diminished when antigen-specific CD8+ T cells were deficient in 2B4. In contrast, 2B4 deficiency had no effect on CD8+ T cell responses during unmodified rejection or in the presence of CTLA-4 Ig. We conclude that blockade of CD28 signals in the presence of preserved CTLA-4 signals results in the unique up-regulation of 2B4 on primary CD8+ effectors, and that this 2B4 expression plays a critical functional role in controlling antigen-specific CD8+ T cell responses. |
| Databáze: | OpenAIRE |
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