Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice.
| Autor: | Hudson KE; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Hendrickson JE, Cadwell CM, Iwakoshi NN, Zimring JC |
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| Jazyk: | angličtina |
| Zdroj: | Haematologica [Haematologica] 2012 Dec; Vol. 97 (12), pp. 1836-44. Date of Electronic Publication: 2012 Jun 24. |
| DOI: | 10.3324/haematol.2012.065144 |
| Abstrakt: | 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: | MEDLINE |
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