Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis
| العنوان: | Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis |
|---|---|
| المؤلفون: | van Herwijnen, M.J.C., Wieten, L., van der Zee, R., van Kooten, P.J., Wagenaar, J.P.A., Hoek, A., den Braber, A.J., Anderton, S.M., Singh, M., Meiring, H.D., van Els, C.A.C.M., van Eden, W., Broere, F., Risk Assessment of Toxic and Immunomodulatory Agents, Strategic Infection Biology, Dep Infectieziekten Immunologie |
| المساهمون: | Risk Assessment of Toxic and Immunomodulatory Agents, Strategic Infection Biology, Dep Infectieziekten Immunologie |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America, 109(35), 14134. National Academy of Sciences Proceedings of the National Academy of Sciences; Vol 109 |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | medicine.medical_treatment, Epitopes, T-Lymphocyte, chemical and pharmacologic phenomena, Autoimmunity, Biology, Lymphocyte Activation, medicine.disease_cause, Autoantigens, Immunotherapy, Adoptive, T-Lymphocytes, Regulatory, Epitope, Autoimmune Diseases, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigen, Stress, Physiological, Immune Tolerance, medicine, Animals, HSP70 Heat-Shock Proteins, IL-2 receptor, Administration, Intranasal, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, MHC class II, Multidisciplinary, Arthritis, FOXP3, Immunotherapy, Biological Sciences, International (not English), Adoptive Transfer, 3. Good health, Arthritis therapy, Immunology, biology.protein, Immunization, 030215 immunology |
| الوصف: | Reestablishing self-tolerance in autoimmunity is thought to depend on self-reactive regulatory T cells (Tregs). Exploiting these antigen-specific regulators is hampered by the obscure nature of disease-relevant autoantigens. We have uncovered potent disease-suppressive Tregs recognizing Heat Shock Protein (Hsp) 70 self-antigens, enabling selective activity in inflamed tissues. Hsp70 is a major contributor to the MHC class II ligandome. Here we show that a conserved Hsp70 epitope (B29) is present in murine MHC class II and that upon transfer, B29-induced CD4 + CD25 + Foxp3 + T cells suppress established proteoglycan-induced arthritis in mice. These self-antigen–specific Tregs were activated in vivo, and when using Lymphocyte Activation Gene-3 as a selection marker, as few as 4,000 cells sufficed. Furthermore, depletion of transferred Tregs abrogated disease suppression. Transferred cells exhibited a stable phenotype and were found in joints and draining lymph nodes up to 2 mo after transfer. Given that ( i ) B29 administration by itself suppressed disease, ( ii ) our findings were made with wild-type (T-cell receptor nontransgenic) Tregs, and ( iii ) the B29 human homolog is presented by HLA class II, we are nearing translation of antigen-specific Treg activation as a promising intervention for chronic inflammatory diseases. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e6d254355422c1d3dfe4faa090294efTest https://dspace.library.uu.nl/handle/1874/274552Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e6d254355422c1d3dfe4faa090294ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00278424 |
|---|