VIP and PACAP enhance the in vivo generation of memory TH2 cells by inhibiting peripheral deletion of antigen-specific effectors.
In an immune response, antigen-specific CD4 T cells proliferate and differentiate into effector cells capable to produce large amounts of cytokines upon restimulation. Most effector T cells are later eliminated through antigen-induced cell death (AICD), mediated through FasL/Fas interactions. A low percentage of effector T cells survive and differentiate into long-lived memory cells. Mechanisms must operate not only to destroy no longer needed and even potentially damaging T cells, but also to allow the survival of a small number of activated T cells. Little is known about the factors and mechanisms that regulate the shift from an apoptosis-sensitive to an apoptosis-resistant phenotype. VIP and the structurally related peptide, PACAP, synthesized and/or released in the immune organs act on both innate and adaptive immunity. Recently, VIP and PACAP were shown to inhibit AICD in peripheral CD4 T cells by down-regulating FasL expression. In view of these findings, VIP and PACAP are reasonable candidates for the generation of memory T cells. To test this hypothesis, we analyzed the effects of VIP and PACAP in various models for effector and memory T cells. Our data demonstrate that both neuropeptides promote the in vivo effector function and memory phenotype of Th2, but not Th1 cells, by preferentially inhibiting the clonal deletion of Th2 cells. To our knowledge, this is the first report describing the role of a neuropeptide present in the lymphoid microenvironment on the generation and maintenance of long-lived memory T cells.
Delgado
M
M
Rutgers University, Newark, NJ, USA. mariodm@eucmos.sim.ucm.es
Ganea
D
D
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism*
C495402:Adcyap1 protein, mouse; D000941:Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide