title: Human regulatory CD8 T cells.
abstract: Administration of a humanized monoclonal anti-CD3 antibody (mAb) to patients with type 1 diabetes (T1D) increases their C-peptide responses and the CD8/CD4 ratio. Incubation of human peripheral blood mononuclear cells (PBMC) with mAb in vitro has been shown to induce CD8(+) regulatory T cells (Tregs) capable of inhibiting proliferation of CD4(+) T cells. We hypothesized that CD8(+) Tregs function through secretion of cytokines. To test that possibility, we generated CD8(+) Tregs, sorted them by FACS, incubated them with syngeneic CD8-depleted PBMC in the presence of staphylococcal enterotoxin B (SEB), and measured proliferation of T cells and cytokines. Using neutralizing anti-cytokine mAbs, we show that the inhibitory effect of CD8(+) Tregs could be partially alleviated by anti-CCL-4, anti-TNF, and to a lesser extent anti-IL2, suggesting that these cytokines contribute to CD8(+) Treg function.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. ablamunits@yale.edu
authors.forename: Vitaly
authors.initials: V
authors.lastname: Ablamunits
authors.forename: Brygida C
authors.initials: BC
authors.lastname: Bisikirska
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D054407:Chemokine CCL4; D016207:Cytokines; D053222:Fas Ligand Protein; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma