Isolation and characterization of human interleukin-10-secreting T cells from peripheral blood.
Recent studies have expanded our understanding of the role of the anti-inflammatory cytokine interleukin (IL)-10, produced by multiple lineages of both human and murine T cells, in regulating the immune response. Here, we demonstrate that the small percentage of circulating CD4(+) T cells that secrete IL-10 can be isolated from human peripheral blood and, importantly, we have optimized a protocol to expand these cells in both antigen-specific and polyclonal manners. Expanded CD4(+)IL-10(+) T cells abrogate proliferation and T helper (Th) 1-like cytokine production in an antigen-specific manner, and to a lesser extent exhibit bystander suppressive capacity. CD4(+)IL-10(+) T cells are suppressive in a cell contact-dependent way, though they do not require secretion of IL-10 for their suppressive role in vitro. CD4(+)IL-10(+) T cells have an activated phenotype, with high expression of CD25, CD69, and cytotoxic T-lymphocyte antigen-4, and are largely FoxP3 negative. This novel method for the isolation and expansion of suppressive IL-10-secreting T cells has important implications both for further research and clinical therapeutic development.
Mazza
Graziella
G
Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Clifton, Bristol, United Kingdom.
Sabatos-Peyton
Catherine A
CA
Protheroe
Rachel E
RE
Herman
Andrew
A
Campbell
John D
JD
Wraith
David C
DC
D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D001775:Blood Circulation / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation
D000941:Antigens; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016753:Interleukin-10