VIP and PACAP inhibit activation induced apoptosis in T lymphocytes.
Apoptosis in T and B lymphocytes is a major element controlling the immune response. Activation induced cell death (AICD) in T cells is a main mechanism for maintaining peripheral tolerance and for limiting an ongoing immune response. AICD is initiated by antigen reengagement of the T cell receptor (TCR), and mediated through Fas/Fas ligand (FasL) interactions. VIP and PACAP are two multifunctional neuropeptides present in the lymphoid microenvironment that act primarily as anti-inflammatory agents. In this study we report on the role of VIP and PACAP on T cell AICD, and on the mechanisms involved. VIP and PACAP inhibit AICD in vivo and in vitro, in peripheral T cells and T cell hybridomas. The effect is dose dependent and is mediated through the specific receptors VPAC1 and VPAC2. The inhibition of AICD is achieved through reduction in FasL expression at protein and mRNA level. By affecting FasL expression, VIP and PACAP may play a physiological role in both the generation of memory T cells and the inhibition of FasL-mediated T cell cytotoxicity.
Delgado
M
M
Departamento Biologia Celular, Facultad de Biologia, Universidad Complutense, Madrid 28040, Spain.
Ganea
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D053222:Fas Ligand Protein; D006825:Hybridomas / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; D017252:CD3 Complex; D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide