Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28- regulatory T cells.
Evidence that T cells can down-regulate the immune response by producing or consuming certain cytokines or by lysing APCs or Th cells has been provided in various systems. However, the generation and characterization of suppressor T cell lines have met with limited success. Here we show that xenospecific suppressor T cells can be generated by in vitro stimulation of human T cells with pig APCs. Similar to allospecific suppressors, these xenospecific suppressor T cells carry the CD8+CD28- phenotype and react to MHC class I Ags expressed by the APCs used for priming. TCR spectratyping of T suppressor cells showed oligoclonal usage of TCR-Vbeta families, indicating that xenostimulation of CD8+CD28- T cells results in Ag-driven selection of a limited Vbeta repertoire. Xenospecific T suppressor cells prevent the up-regulation of CD154 molecules on the membrane of Th cells, inhibiting their ability to react against the immunizing MHC class II xenoantigens. The mechanism of this suppression, therefore, appears to be blockade of CD154/CD40 interaction required for efficient costimulation of activated T cells.
Ciubotariu
R
R
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York 10032, USA.
Colovai
A I
AI
Pennesi
G
G
Liu
Z
Z
Smith
D
D
Berlocco
P
P
Cortesini
R
R
Suciu-Foca
N
N
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D013552:Swine; D013556:Swine, Miniature; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D015478:Antigens, Heterophile; D018106:CD28 Antigens; D019013:CD40 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D006649:Histocompatibility Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D023201:CD40 Ligand