HUMAN NAIVE T-CELLS ACTIVATED BY CYTOKINES DIFFERENTIATE INTO A SPLITPHENOTYPE WITH FUNCTIONAL FEATURES INTERMEDIATE BETWEEN NAIVE AND MEMORY T-CELLS

We have recently shown that CD45RA(+)CD4(+) naive T cells can be activ ated to proliferate by a combination of IL-2, TNF-alpha and IL-6, but, at variance with TCR-mediated activation, they do not acquire the CD4 5RO molecule, This prompted us to investigate the phenotype of these c ells and the functional features they display upon TCR stimulation, Na ive T cells expanded by cytokines, though remaining CD45RA(+), express a variety of activation and adhesion molecules which are peculiar to effector or memory T cells, Naive cells primed by cytokines, when acti vated with anti-CD3 mAb, produce a broad spectrum of cytokines, expres s CD40 ligand, but are unable to help a cells for Ig synthesis, A subs et of CD4(+)CD45RA(+)RO(-) T cells with a phenotype (HLA-DR(-), VLB-2( +) or IL-2R(+)) similar to that of cells activated by cytokines in vit ro can be found in vivo, These results demonstrate that activation sig nals delivered by cytokines, in the absence of TCR stimulation, can ac tivate naive T cells to proliferate and differentiate into a 'split ph enotype' with elements common to both naive and memory T cells, This n ovel antigen-independent activation may help to maintain the naive T c ell repertoire and facilitate the antigen-responsiveness of naive T ce lls.