Neonatal tolerance to a Th2-mediated autoimmune disease generates CD8+ Tc1 regulatory cells.
Immunological tolerance can be achieved in animals by exposure of newborn to a foreign antigen. Depending on the dose and timing of the antigenic challenge, tolerance has been reported to result in clonal deletion, anergy or active suppression. In this latter case, regulatory T cells prevent autoimmunity by suppressing the reactivity of pathogenic self-reactive T cells. We have previously reported the generation of a neonatal, mercury-specific, and dominant tolerance to autoimmunity induced by mercury salts in rats. Chronic exposure to mercury salts can lead to SLE-like autoimmune responses, mediated by autoreactive CD4+ Th2 cells, that regulate and are followed by a resistant state mediated by protective CD8+ T cells. The aim of the study was to compare the resistance to the neonatal tolerance to mercury disease, and to further characterize the CD8+ T cells endowed with regulatory capacity in the neonatal tolerance model. We report here that resistance to mercury disease is long lasting and not mercury-specific, suggesting that different CD8+ T cells are involved in resistance and neonatal tolerance, and that regulatory CD8+ Tc1 cells generated in tolerance are required to control the CD8- cell population from developing Th2-mediated autoimmunity. Upon mercury recall, CD8+ CD45RC(high) T cells, that represent the Tc1 subset in the rat, expanded and were polarized towards IFNgamma production. Interestingly, identical results were obtained with the CD8+ CD25+T cell population. Substantial amounts of FasL gene expression were detected in CD8+ T lymphocytes upon recall with the tolerogen. AICD may be one of the regulatory mechanisms used by these regulatory CD8+ Tc1 cells that control neonatal tolerance to a Th2-mediated autoimmune disorder.
Institut National de la Santé et de la Recherche Médicale U430, Immunopathologie Humaine, 15 rue de l'Ecole de Médecine, 75270 Cedex 06, Paris, France. anne-christine.field@u430.bhdc.jussieu.fr
Anne-Christine
AC
Field
Marie-Françoise
MF
Bloch
Blanche
B
Bellon
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004112:Dimercaprol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D053222:Fas Ligand Protein; D015870:Gene Expression; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D017710:Lymphocyte Transfusion; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000276:immunology; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D020005:Propanols; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013438:Sulfhydryl Compounds; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D015375:Receptors, Interleukin-2; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; C013394:aurotioprol