STABLE POLARIZATION OF PERIPHERAL-BLOOD T-CELLS TOWARDS TYPE-1 OR TYPE-2 PHENOTYPE AFTER POLYCLONAL ACTIVATION

Citation
S. Asselin et al., STABLE POLARIZATION OF PERIPHERAL-BLOOD T-CELLS TOWARDS TYPE-1 OR TYPE-2 PHENOTYPE AFTER POLYCLONAL ACTIVATION, European Journal of Immunology, 28(2), 1998, pp. 532-539
Citations number
19
Categorie Soggetti
Immunology
ISSN journal
00142980
Volume
28
Issue
2
Year of publication
1998
Pages
532 - 539
Database
ISI
SICI code
0014-2980(1998)28:2<532:SPOPTT>2.0.ZU;2-9
Abstract
Polarization of T lymphocytes towards type 1 (TI) or type 2 (T2) subse ts producing a distinct array of cytokines plays a role in several dis eases and could be used for therapeutic intervention. Bearing this pur pose in mind, we have established suitable in vitro conditions to driv e resting polyclonal human T cells towards stable T1 or T2 polarizatio n profiles. Unselected peripheral lymphocytes from normal donors were primed with soluble anti-CD3 monoclonal antibody in the presence of se lected 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 l evels. 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 induc ed a shift towards a T1 pattern characterized by increased productions of IFN-gamma and IL-2. Strikingly, the T2 profile appeared more stabl e in culture than the T1 profile. We also observed that the CD4(+) hel per T cell subset was the major producer of T1 and T2 cytokines after restimulation. These results establish in vitro parameters to delibera tely and reproducibly activate resting polyclonal T cells towards a de fined and persistent cytokine secretion profile. Autologous T cells po larized under these conditions could be passively transferred as a the rapeutic approach in diseases thought to result from imbalance between T1 and T2 responses.