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 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.
Varthaman
Aditi
A
Institut National de la Santé et de la Recherche Médicale U698, France.
Khallou-Laschet
Jamila
J
Clement
Marc
M
Fornasa
Giulia
G
Kim
Hye-Jung
HJ
Gaston
Anh-Thu
AT
Dussiot
Michael
M
Caligiuri
Giuseppina
G
Herbelin
André
A
Kaveri
Srinivas
S
Cantor
Harvey
H
Nicoletti
Antonino
A
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003208:Concanavalin A / Q000276:immunology / Q000633:toxicity; D005434:Flow Cytometry; D006505:Hepatitis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008934:Mitogens / Q000276:immunology / Q000633:toxicity; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000637:transplantation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination
D015395:Histocompatibility Antigens Class I; D008934:Mitogens; C032907:Q surface antigens; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A