Cell surface expression of CD154 inhibits alloantibody responses: A mechanism for the prevention of autoimmune responses against activated T cells?
Binding of CD40 by CD154 expressed on activated T cells is a pivotal event in T cell help to B cells, macrophages, and other antigen-presenting cells. Expression of CD154 by MHC mismatched cells, in contrast to expectations, strongly suppressed alloantibody responses against the cells. This was caused by a failure of priming of antibody responses by the CD154 expressing cells. We hypothesize that this lack of response against CD154 expressing cells may represent a mechanism that has evolved to prevent autoantibody responses being generated against the CD154 antigen itself, as B cells expressing antibody reactive with CD154 would probably escape deletion on binding antigen in the bone marrow due to rescue by the simultaneous ligation of CD40.
McCormick
A L
AL
Division of Molecular and Genetic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom.
Santos-Argumedo
L
L
Thomas
M S
MS
Heath
A W
AW
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D023201:CD40 Ligand; D005260:Female; D015870:Gene Expression; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007518:Isoantibodies / Q000276:immunology*; D007739:L Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014162:Transfection
D000906:Antibodies; D007518:Isoantibodies; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester