Specificity of regulatory CD4+CD25+ T cells for self-T cell receptor determinants.
Although the phenotypic and regulatory properties of the CD4(+)CD25(+) T cell lineage (Treg cells) have been well described, the specificities remain largely unknown. We demonstrate here that the CD4(+)CD25(+) Treg population includes the recognition of a broad spectrum of human TCR CDR2 determinants found in the germline V gene repertoire as well as that of a clonotypic nongermline-encoded CDR3beta sequence present in a recombinant soluble T cell receptor (TCR) protein. Regulatory activity was demonstrated in T cell lines responsive to TCR but not in T cell lines responsive to control antigens. Inhibitory activity of TCR-reactive T cells required cell-cell contact and involved CTLA-4, GITR, IL-10, and IL-17. Thus, the T-T regulatory network includes Treg cells with specificity directed toward self-TCR determinants.
Buenafe
Abigail C
AC
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA. buenafea@ohsu.edu
Tsaknaridis
Laura
L
Spencer
Leslie
L
Hicks
Kevin S
KS
McMahan
Rachel H
RH
Watson
Lisa
L
Culbertson
Nicole E
NE
Latocha
Dorian
D
Wegmann
Keith
K
Finn
Tom
T
Bartholomew
Richard
R
Burrows
Gregory G
GG
Whitham
Ruth
R
Bourdette
Dennis N
DN
Jones
Richard E
RE
Offner
Halina
H
Chou
Yuan K
YK
Vandenbark
Arthur A
AA
D019138:Antibodies, Blocking / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D003001:Cloning, Molecular; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000502:physiology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D007165:Immunosuppression Therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016622:Silver Staining
D019138:Antibodies, Blocking; D016207:Cytokines; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins