Supplement of IL-4 and CD4+CD25+ cells successfully retards the development of AIHA in NZB mice

• Main Authors: Chang Chia-Ching, 張家菁
• Other Authors: Shen Chia-Rui
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/56263501419630475957

碩士 === 長庚大學 === 醫學生物技術研究所 === 94 === New Zealand Black (NZB) mice spontaneously develop autoimmune hemolytic anemia (AIHA). Previous studies from our laboratories show that the predominant Th1-responses including high levels of IFN-γ produced by T cells in response to the autoantigen Band 3. Inhalation of a soluble analog (Glu861, Lys875) of Band 3 peptide 861-874, which contains a dominant autoreactive helper T-cell epitope, was able to modulate the course of AIHA in NZB mice by deviating the autoimmune responses toward a Th2 profile, particularly that a high level of IL-4 was produced by T cells responding in vitro to Band 3. Therefore, in this study I have further identified the role of IL-4 in the development of NZB AIHA. It is shown that the erythrocyte autoantibodies were only present on the RBCs from 2 out of 9 NZB animals treated with IL-4 gene for 15 weeks, while relatively higher levels of those antibodies were found in all the animals treated with vector control only or without any treatment. Additionally, the IL-4 treatment has promoted the expression of CD4+CD25+Foxp3+ T cells among the splenocytes of NZB mice. Adoptive transfer of CD4+CD25+ cells, which express high levels of Foxp3, purified from BALB/c animals significantly increased the dropped hematocrit values as well as to reduced the titers of RBC bound autoantibodies in anemic NZB mice. These CD4+CD25+ cells as compared to CD4+CD25- cells bear weaken ability to proliferate in response to anti-CD3 and anti-CD28 stimulation. However, significantly higher levels of IL-10, IL-4 and IFN-γ were produced by these cells. It appeared that not only IL-10 but also other cytokines can be produced abundantly by CD4+CD25+ cells. Taken together, IL-4 treatment able to retard the NZB AIHA development may results from the induction of CD4+CD25+ cells.