TY - JOUR
T1 - Control of T cell reactivation by regulatory Qa-1-restricted CD8 + T cells
AU - Varthaman, Aditi
AU - Khallou-Laschet, Jamila
AU - Clement, Marc
AU - Fornasa, Giulia
AU - Kim, Hye Jung
AU - Gaston, Anh Thu
AU - Dussiot, Michael
AU - Caligiuri, Giuseppina
AU - Herbelin, André
AU - Kaveri, Srinivas
AU - Cantor, Harvey
AU - Nicoletti, Antonino
PY - 2010/6/15
Y1 - 2010/6/15
N2 - Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8+ T cells specific for peptides derived from the Vβ-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 Vβ-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 Vβ-chains irrelevant to NKT cells, we discovered that the specificity of vaccine-induced Qa-1-restricted CD8 + T cells was not limited to the Vβ-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.
AB - Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8+ T cells specific for peptides derived from the Vβ-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 Vβ-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 Vβ-chains irrelevant to NKT cells, we discovered that the specificity of vaccine-induced Qa-1-restricted CD8 + T cells was not limited to the Vβ-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.
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U2 - 10.4049/jimmunol.0903109
DO - 10.4049/jimmunol.0903109
M3 - Article
C2 - 20488793
AN - SCOPUS:77953635469
VL - 184
SP - 6585
EP - 6591
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -