TCRalphabeta repertoire diversity of human naturally occurring CD4+CD25+ regulatory T cells.
We examined the alphabeta T cell receptor (TCR) repertoire of naturally occurring CD4+CD25+ regulatory T (Treg) cells isolated from healthy human blood. Three-color FACS analysis demonstrated that the usage of variable region segments of TCRbeta chains by CD4+CD25+ cells did not differ from those of CD4+CD25- cells. Complementarity-determining region 3 (CDR3) size distribution analyses demonstrated that the repertoire diversity of CDR3beta was almost identical between CD4+CD25+ and CD4+CD25- T cell subsets, and that there was no skewing of the CDR3beta repertoire of CD4+CD25+ T cells. In contrast, in vitro activated CD4+CD25+ T cells by cytomegalovirus-derived antigens showed a skewed CDR3 size distribution pattern. These findings support the hypothesis that naturally occurring CD4+CD25+ T cell subset in humans is 1argely composed of a T cell lineage positively selected in the thymus as a consequence of the interaction between self-peptides and TCRs and not derived from recent activation by a limited array of antigens.
Fujishima
Masumi
M
Division of Hematology and Oncology, Department of Medicine III, Akita University School of Medicine, Japan.
Hirokawa
Makoto
M
Fujishima
Naohito
N
Sawada
Ken-ichi
K
D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D022801:Complementarity Determining Regions / Q000276:immunology; D018076:DNA, Complementary / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D006801:Humans; D018189:Immunomagnetic Separation; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
D015704:CD4 Antigens; D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2