Regulatory CD8+ T cells control neonatal tolerance to a Th2-mediated autoimmunity.
Exposure of newborn animals to a foreign Ag may result in immunological tolerance to that specific Ag, a phenomenon called neonatal tolerance. We have previously reported that neonatal administration to Brown-Norway rats of mercury, a heavy metal toxicant, induces a dominant tolerance, specific for the chemical otherwise responsible for Th2 cell-mediated autoimmune responses in this susceptible strain of rats. Neonatal exposure to Ags can prime immunity, rather than inactivate or delete responses, and sustain regulatory functions effective against autoreactive T cells. Here, we address whether such a tolerant response is due to the generation of regulatory cells. The results suggest that the CD8(+) T cell subset is involved in neonatal tolerance to mercuric salt-induced Th2 autoimmune disease. Thus, we demonstrate that in vivo CD8 depletion breaks tolerance following mercury recall in animals under a neonatal tolerance protocol. Furthermore, adoptive cotransfer of splenocytes from naive and tolerant rats as well as transfer of CD8(+) T cells from tolerant animals prevent naive syngeneic rats from developing pathologic Th2 immune responses. These observations indicate that CD8(+) T cells are endowed with regulatory functions in neonatal tolerance and mediate active suppression. Moreover, neonatal tolerance induced the expansion of CD8(+)CD45RC(high) T cells and the emergence of a high percentage of IFN-gamma-synthesizing CD8(+) T cells, which probably reflects the implication of regulatory Tc1 cells. Thus, in vivo induction of neonatal tolerance suppresses Th2 autoimmune responses via generation of a CD8(+) cell-mediated regulatory response.
Field
Anne-Christine
AC
Institut National de la Santé et de la Recherche Médicale, Unité 430, Immunopathologie Humaine, Institut des Cordeliers, Paris, France.
Caccavelli
Laure
L
Bloch
Marie-Françoise
MF
Bellon
Blanche
B
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000187:drug effects; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D016207:Cytokines; D008627:Mercuric Chloride