Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation

• Published in: Trends in immunology Vol. 32; no. 9; pp. 428 - 433
• Main Authors: Wing, Kajsa, Yamaguchi, Tomoyuki, Sakaguchi, Shimon
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2011; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibodies, Neutralizing - pharmacology; antigen-presenting cells; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; antigens; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmune Diseases - therapy; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; Cell Communication - immunology; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - deficiency; CTLA-4 Antigen - genetics; cytotoxicity; Disease; Forkhead Transcription Factors - immunology; Genes; Homeostasis; Homeostasis - immunology; immune response; Immune system; Immune Tolerance - drug effects; Immunity; Immunotherapy - methods; Ligands; Lymphocyte Activation - immunology; Lymphocytes; Medicin och hälsovetenskap; Mice; Mice, Knockout; Rodents; Signal Transduction - immunology; T cell receptors; T-lymphocytes; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 1471-4906; 1471-4981; 1471-4981
• DOI: 10.1016/j.it.2011.06.002

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.