Human peripheral gammadelta T cells possess regulatory potential.
Deficiency in gammadelta T cells aggravates colitis in animal models suggesting that gammadelta T cells have regulatory properties. Therefore, proliferation, suppression and cytokine secretion of human gammadelta T cells were determined in vitro. Human peripheral gammadelta T cells were isolated from the whole blood of healthy donors by magnetic antibody cell sorting technology. The proliferation after CD3/CD28 stimulation was measured by (3)[H]thymidine incorporation. Interferon-gamma (IFN-gamma), interleukin-2 (IL-2), transforming growth factor-beta (TGF-beta) and IL-10 concentrations were measured by enzyme-linked immunosorbent assay; TGF-beta messenger RNA was also measured by reverse transcription-polymerase chain reaction. The expression of latency associated peptide (LAP), a TGF-beta complex component, intracellular cytokine content and T helper cell proliferation were measured by flow cytometry. Human gammadelta T cells showed poor proliferation upon CD3/CD28 stimulation and suppressed T helper cell growth stronger than CD4(+) CD25(+) T cells, although gammadelta T cells were FOXP3 negative. They secreted little IL-2 but high concentrations of IFN-gamma, IL-10 and TGF-beta. When looking at LAP expression the Vdelta1 subset was found to be the main TGF-beta producer compared to Vdelta2 T cells. Taken together, peripheral gammadelta T cells have in vitro a more potent regulatory potential than CD4(+) CD25(+) cells regarding T helper cell suppression. This is most likely the result of strong TGF-beta secretion, particularly by the Vdelta1 subset.
Kühl
Anja A
AA
Medizinische Klinik I, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany.
Pawlowski
Nina N
NN
Grollich
Katja
K
Blessenohl
Maike
M
Westermann
Jürgen
J
Zeitz
Martin
M
Loddenkemper
Christoph
C
Hoffmann
Jörg C
JC
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D016207:Cytokines; D018836:Inflammation Mediators; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016212:Transforming Growth Factor beta