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

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 capac...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-06, Vol.184 (12), p.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: Article
Language:English
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0903109