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Updated: Apr 23, 2026
Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
CTLA4-Ig preserves thymus-derived T regulatory cells
Sarah M Ahmadi1, Markus A Hölzl, Edda Mayer
11 Division Transplantation Immunology, Children's Cancer Research Institute, Vienna, Austria. 2 Division of Transplantation, Department of Surgery, Medical University Vienna, Austria. 3 Address correspondence to: Sarah Ahmadi, M.Sc., Children's Cancer Research Institute, Zimmermannplatz 10, A-1090 Vienna, Austria.
Background:
CTLA-4 immunoglobulin fusion proteins (CTLA4-Ig) suppress immune reactions by blocking the T-cell costimulatory CD28-CD80-86 pathway and are used in clinical trials for diseases featuring exaggerated T-cell reactivity including autoimmune diseases and allograft rejection. However, because CTLA4-Ig has been suspected to interfere with T regulatory (Treg) cell homeostasis and function, recently, substantial concerns on CTLA4-Ig's potentially antitolerogenic effects have been raised.
Methods:
We tested immunoregulatory CTLA4-Ig explicitly for its effect on Treg cell numbers, frequencies and function in an in vitro murine major histocompatibility complex mismatched setting using C57BL/6 bone marrow-derived dendritic cells as stimulators of allogeneic Balb/c Foxp3 T cells, which allowed for tracing Treg cells in a straightforward fashion.
Results:
The presence of CTLA4-Ig in mixed leukocyte reactions-while dampening the global proliferative response of allostimulated Balb/c T cells-resulted in a relative increase of the frequency of thymus-derived CD4CD25Foxp3 Treg cells with intact suppressive activity. This relative increase was caused by a selective inhibitory effect of CTLA4-Ig on proliferating conventional T cells, whereas the proliferative capacity of Treg cells in cell cultures remained unaffected. Additionally, in the presence of CTLA4-Ig, the frequency of apoptosis was decreased in these cells.
Conclusion:
Our findings unequivocally demonstrate that CTLA4-Ig does not negatively affect Treg cell frequencies and function in vitro.
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