Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

• Published in: The Journal of immunology (1950) 2003-03, Vol.170 (5), p.2508-2515
• Main Authors: Field, Anne-Christine, Caccavelli, Laure, Bloch, Marie-Francoise, Bellon, Blanche
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Animals, Newborn - immunology; Antibodies, Monoclonal - administration & dosage; Autoimmune Diseases - chemically induced; Autoimmune Diseases - immunology; CD8 Antigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - transplantation; Cytokines - biosynthesis; Disease Models, Animal; Immune Tolerance - drug effects; Immunophenotyping; Injections, Subcutaneous; Intracellular Fluid - immunology; Intracellular Fluid - metabolism; Male; Mercuric Chloride - administration & dosage; Mercuric Chloride - immunology; Rats; Rats, Inbred BN; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; Th2 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.5.2508

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.