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
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.