IN-VITRO DIFFERENTIATION OF PERIPHERAL-BLOOD T-CELLS TOWARDS A TYPE-2PHENOTYPE IS IMPAIRED IN RHEUMATOID-ARTHRITIS (RA)

We have examined the capacity of peripheral blood T cells from RA pati ents to be polarized in in vitro towards a type I (TI) or a type 2 (T2 ) phenotype. Peripheral blood T cells from RA patients and from health y donors were primed by 1 week of culture with soluble OKT3 in the pre sence of polarizing cytokines. The recovered T cells were restimulated and their cytokine secretion profile determined. Priming of T cells f rom RA patients in the presence of recombinant (r)IL-2 plus rIL-12 ind uced a shift towards a T1 pattern, characterized by increased producti on of interferon-gamma, that was more pronounced than in the case of h ealthy donors. Conversely, priming of T cells from RA patients in the presence of IL-4 failed to induce a shift towards a T2 profile after 1 week, whereas it induced T cells from healthy donors to acquire such a profile characterized by heightened production of IL-4, IL-5 and IL- 13. However, it T2 polarization profile emerged in T cells from RA pat ients that were primed in the presence of rIL-4 and subsequently maint ained in culture in rIL-2 alone for 1 or 2 additional weeks. We conclu de that in vitro differentiation of peripheral T cells towards a type 2 phenotype is impaired in RA. Nevertheless, conditions required to dr ive peripheral T cells towards a type 2 phenotype were established. Ad ministration of autologous polyclonal T cells expressing a type 2 cyto kine secretion profile is proposed as a therapeutic strategy in RA.