Regulation of immunity by a novel population of Qa-1-restricted CD8alphaalpha+TCRalphabeta+ T cells.
Regulatory mechanisms involving CD8+ T cells (CD8 regulatory T cells (Tregs)) are important in the maintenance of immune homeostasis. However, the inability to generate functional CD8 Treg clones with defined Ag specificity has precluded a direct demonstration of CD8 Treg-mediated regulation. In the present study, we describe the isolation of functional lines and clones representing a novel population of TCRalphabeta+ Tregs that control activated Vbeta8.2+ CD4 T cells mediating experimental autoimmune encephalomyelitis. They express exclusively the CD8alphaalpha homodimer and recognize a peptide from a conserved region of the TCR Vbeta8.2 chain in the context of the Qa-1a (CD8alphaalpha Tregs). They secrete type 1 cytokines but not IL-2. CD8alphaalpha Tregs kill activated Vbeta8.2+ but not Vbeta8.2- or naive T cells. The CD8alphaalpha Tregs prevent autoimmunity upon adoptive transfer or following in vivo activation. These findings reveal an important negative feedback regulatory mechanism targeting activated T cells and have implications in the development of therapeutic strategies for autoimmune diseases and transplantation.
Tang
Xiaolei
X
Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Maricic
Igor
I
Purohit
Nikunj
N
Bakamjian
Berge
B
Reed-Loisel
Lisa M
LM
Beeston
Tara
T
Jensen
Peter
P
Kumar
Vipin
V
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta