Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice
| Autor: | Jeanne E. Hendrickson, James C. Zimring, Krystalyn E. Hudson, Chantel M. Cadwell, Neal N. Iwakoshi |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adoptive cell transfer
Erythrocytes T-Lymphocytes Autoantigens Epitope Immune tolerance Mice Immune system Antigen Immune Tolerance medicine Animals Humans B-Lymphocytes Mice Inbred BALB C biology Autoantibody Hematology Flow Cytometry medicine.disease Mice Inbred C57BL Ovalbumin Immunology biology.protein Muramidase Original Articles and Brief Reports Autoimmune hemolytic anemia |
| Zdroj: | Haematologica. 97:1836-1844 |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2012.065144 |
| Popis: | Background Breakdown of humoral tolerance to RBC antigens may lead to autoimmune hemolytic anemia, a severe and sometimes fatal disease. The underlying mechanisms behind the breakdown of humoral tolerance to RBC antigens are poorly understood. Design and Methods In order to study the pathogenesis of autoimmune hemolytic anemia, we developed a murine model with RBC-specific expression of a model antigen carrying epitopes from hen egg lysozyme and ovalbumin. Results Humoral tolerance was observed; this was not broken even by strong immunogenic stimulation (lysozyme or ovalbumin with adjuvant). Autoreactive CD4+ T cells were detected by tetramer enrichment assays, but failed to activate or expand despite repeat stimulation, indicating a nonresponsive population rather than deletion. Adoptive transfer of autoreactive CD4+ T cells (OT-II mice) led to autoantibody (anti-lysozyme) production by B cells in multiple anatomic compartments, including the bone marrow. Conclusions These data demonstrate that B cells autoreactive to RBC antigens survive in healthy mice with normal immune systems. Furthermore, autoreactive B cells are not centrally tolerized and are receptive to T-cell help. As the autoreactive T cells are present but non-responsive, these data indicate that factors that reverse T-cell non-responsiveness may be central to the pathogenesis of autoimmune hemolytic anemia. |
| Databáze: | OpenAIRE |
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