title: Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation.
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.
authors: Section of Medical Inflammation Research, Department of Medical Biophysics and Biochemistry, Karolinska Institute, Stockholm, Sweden.
authors: Kajsa
authors: K
authors: Wing
authors: Tomoyuki
authors: T
authors: Yamaguchi
authors: Shimon
authors: S
authors: Sakaguchi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D002450:Cell Communication / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007109:Immunity; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse