Umbilical cord blood T cells respond against the Melan-A/MART-1 tumor antigen and exhibit reduced alloreactivity as compared with adult blood-derived T cells.
Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells to treat a variety of disorders. UCB transplant is associated with comparatively reduced incidence of graft-versus-host disease, robust graft versus leukemia effect, and relatively high incidence of opportunistic infections, three processes in which donor-derived T lymphocytes are known to be predominantly involved. To examine the differential functionality of UCB T cells, CD8(+) T cells specific for the melanoma-associated HLA-A2-restricted Melan-A(26-35) A27L peptide were isolated from HLA-A2(+) and HLA-A2(-) UCB samples and HLA-A2(+) and HLA-A2(-) adult peripheral blood using A2/Melan-A tetramers. In UCB samples, A2/Melan-A(+) CD8(+) T cells were detected at a frequency of 0.04%, were more frequent in HLA-A2(+) UCB, and were polyclonal and mostly naive. Consistent with Ag-driven expansion, the frequency of A2/Melan-A(+) CD8(+) T cells was increased following stimulation with cognate peptide or polyclonal activation, they acquired cell-surface markers reflective of effector/memory differentiation, their TCR repertoire became oligoclonal, and they expressed cytolytic activity and produced IFN-gamma. Although functional properties of A2/Melan-A(+) CD8(+) T cells derived from HLA-A2(+) UCB resembled those of HLA-A2(+) adult peripheral blood, they were more likely to reach terminal differentiation following polyclonal stimulation and produced less IFN-gamma in response to cognate peptide. A2/Melan-A(+) CD8(+) T cells from HLA-A2(-) UCB were poorly cytolytic, produced little IFN-gamma, and were predominantly monofunctional or nonfunctional. These properties of UCB-derived CD8(+) T cells could contribute to the reduced incidence of graft-versus-host disease and heightened incidence of opportunistic infections observed following UCB transplant.
Merindol
Natacha
N
Unité d'Immunopathologie Virale, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
Grenier
Anne-Julie
AJ
Caty
Martine
M
Charrier
Emily
E
Duval
Arnaud
A
Duval
Michel
M
Champagne
Martin A
MA
Soudeyns
Hugo
H
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma