Stable polarization of peripheral blood T cells towards type 1 or type 2 phenotype after polyclonal activation.
Polarization of T lymphocytes towards type 1 (T1) or type 2 (T2) subsets producing a distinct array of cytokines plays a role in several diseases and could be used for therapeutic intervention. Bearing this purpose in mind, we have established suitable in vitro conditions to drive resting polyclonal human T cells towards stable T1 or T2 polarization profiles. Unselected peripheral lymphocytes from normal donors were primed with soluble anti-CD3 monoclonal antibody in the presence of selected sets of recombinant (r) human cytokines. Following this priming process the cytokine secretion profiles of the recovered T cells were assayed after restimulation, both at the population and single-cell levels. A marked shift towards T2 profile, characterized by heightened production of IL-4, IL-5 and IL-13, was obtained after priming in the presence of rIL-4 alone. Addition of rIL-2 partially antagonized this effect. In contrast, priming in the presence of rIL-2 and rIL-12 induced a shift towards a T1 pattern characterized by increased productions of IFN-gamma and IL-2. Strikingly, the T2 profile appeared more stable in culture than the T1 profile. We also observed that the CD4+ helper T cell subset was the major producer of T1 and T2 cytokines after restimulation. These results establish in vitro parameters to deliberately and reproducibly activate resting polyclonal T cells towards a defined and persistent cytokine secretion profile. Autologous T cells polarized under these conditions could be passively transferred as a therapeutic approach in diseases thought to result from imbalance between T1 and T2 responses.
Asselin
S
S
INSERM U477, Hôpital Cochin, Université René Descartes, Paris, France.
Conjeaud
H
H
Minty
A
A
Fradelizi
D
D
Breban
M
M
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma