| Summary: | 碩士 === 長庚大學 === 醫學生物技術研究所 === 96 === Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. However, it remains unclear that the function or number of Treg is directly associated with the development of autoimmune diseases with aberrant antibody production or antibody secreting cells (ASC). New Zealand Black (NZB) mice spontaneously developing erythrocyte autoantibodies, leading to autoimmune hemolytic anemia (AIHA) provide a good animal model to study the antibody dependent autoimmune disease. In this study, we attempted to investigate whether Treg plays a role in the NZB disease development and in controlling (auto)antibody production or the numbers of plasma cells. First, the phenotypic analysis of splenocytes revealed a increased number of regulatory T (Treg)-like (CD4+CD25+) cells as well as a high frequency of plasma cells following the enhanced titers of RBC-bound autoantibodies in disease mice. To characterize these elevated CD4+CD25+ cells, expression of the other molecules associated with Treg, including Foxp3, GITR, FR4 and CD62L, was analyzed. Compared to those pre-onset animals, although the disease mice harbored an increased number of CD4+CD25+Foxp3+ cells, such cells appeared to be in their activated status by phenotypic expression of CD4+CD25+CD62L- and CD4+FR4-CD25+. By using purified CD4+CD25+ cells from non-autoimmune BALB/c mice cocultured with splenocytes, we showed that CD4+CD25+ were able to reduce the antibody production and the number of ASC. The ongoing experiment will clarify whether NZB CD4+CD25+ cells would behave like those in BALB/c mice. Moreover, our earlier study showed that the autoantigen band3 peptide 861-870 containing a dominant autoreactive helper T-cell epitope was able in vivo to modulate the course of AIHA in NZB mice. Here we found that such treatment not only suppressed the erythrocyte autoantibody production, but also reduced plasma cells soon after the mice received peptide treatment. In fact, the reduction of activating T cells (CD4+FR4-CD25+) was also noted. These findings provide us more information of T and B cell subsets orchestrating in NZB disease development. Particularly, the finding that BALB/c CD4+CD25+ cells were able to suppress antibody production in NZB animal explains our recent result, in which adoptive transfer of BALB/c CD4+CD25+ cells successfully reduced the production of erythrocyte autoantibody. Altogether, the above findings benefit the further studies of understanding NZB disease as well as the T regulatory cell biology interacting with B cells.
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