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Updated: May 31, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation
Kajsa Wing1, Tomoyuki Yamaguchi, Shimon Sakaguchi
1Section of Medical Inflammation Research, Department of Medical Biophysics and Biochemistry, Karolinska Institute, Stockholm, Sweden.
Abstract:
It is controversial how cytotoxic T lymphocyte antigen (CTLA)-4, a co-inhibitory molecule, contributes to immunological tolerance and negative control of immune responses. Its role as an inducer of cell-intrinsic negative signals to activated effector T cells is well documented. However, there is accumulating evidence that CTLA-4 is essential for the function of naturally occurring Foxp3(+) regulatory T (Treg) cells, which constitutively express the molecule. CTLA-4 deficiency in Foxp3(+) Treg cells indeed impairs their in vivo and in vitro suppressive function. Further, Treg cells can modulate the function of CD80- and CD86-expressing antigen-presenting cells via CTLA-4. Here we discuss how CTLA-4 expression by one T cell can influence the activation of another in a cell non-autonomous fashion and thus control immune responses.
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