Control of T cell reactivation by regulatory Qa-1-restricted CD8+ T cells

• Published in: The Journal of immunology (1950) Vol. 184; no. 12; pp. 6585 - 6591
• Main Authors: Varthaman, Aditi, Khallou-Laschet, Jamila, Clement, Marc, Fornasa, Giulia, Kim, Hye-Jung, Gaston, Anh-Thu, Dussiot, Michael, Caligiuri, Giuseppina, Herbelin, André, Kaveri, Srinivas, Cantor, Harvey, Nicoletti, Antonino
• Format: Journal Article
• Language: English
• Published: United States Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 15.06.2010
• Subjects: Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes - immunology; Cell Separation; Concanavalin A - immunology; Concanavalin A - toxicity; Flow Cytometry; Hepatitis - immunology; Histocompatibility Antigens Class I - immunology; Immunology; Life Sciences; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mitogens - immunology; Mitogens - toxicity; Natural Killer T-Cells - immunology; Natural Killer T-Cells - transplantation; Receptors, Antigen, T-Cell - immunology; T-Lymphocyte Subsets - immunology; Vaccination
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903109

Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8+ T cells specific for peptides derived from the Vbeta-chain of the TCR presented by the MHC class Ib molecule, Qa-1 expressed on the vaccine cells. These regulatory CD8+ T cells have the capacity to control the activation of endogenous T cells expressing the same TCR Vbeta-chain as the vaccinating cells. We hypothesized that vaccination with NKT cells could also induce Qa-1-restricted CD8+ T cells that would control NKT cell activation. We tested this hypothesis in a murine model of Con A-induced hepatitis that is induced by NKT cells. Vaccination with NKT cells effectively induced protective Qa-1-restricted CD8+ T cells that prevented hepatitis. Surprisingly, upon vaccination with T cells expressing Vbeta-chains irrelevant to NKT cells, we discovered that the specificity of vaccine-induced Qa-1-restricted CD8+ T cells was not limited to the Vbeta-chain of the vaccinating cells. We further show that these regulatory Qa-1-restricted CD8+ T cells arise spontaneously upon polyclonal activation of T cells in the absence of deliberate T cell vaccination. These experiments provide new insight into a CD8+ T cell compartment that regulates the immediate reactivation of conventional T cells and NKT cells.