LEUKEMIC T-CELLS FROM PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA DEMONSTRATE ENHANCED ACTIVATION THROUGH CDW60, CD2, AND CD28 RELATIVE TO ACTIVATION THROUGH THE T-CELL ANTIGEN RECEPTOR COMPLEX

Antigen-dependent activation of T cells occurs through the T-cell anti gen-receptor complex (TCR/CD3). Antigen-independent T-cell activation may occur through the surface molecules CDw60, CD2, and CD28. We wishe d to determine whether these antigen-independent T-cell - activation p athways could be involved in proliferation of leukemic T cells from pa tients with cutaneous T-cell lymphoma (CTCL). Whereas CDw60 was only e xpressed on 28% +/- 7% (mean +/- SEM) of blood T cells obtained from h ealthy control subjects (n = 4), CDw60 was expressed on 94% 3% of bloo d T cells obtained from patients with CTCL (n 4). Dual color immunoflu orescence microscopy of the T-cell infiltrate in involved skin of thes e patients demonstrated that almost 100% of the T cells expressed CDw6 0. Not only did T cells in the patients with CTCL express CDw60, but t riggering of the T cells with anti-CDw60 resulted in enhanced prolifer ation relative to anti-TCR/CD3 and mitogenic lectins. Other antigen-in dependent pathways also appeared highly active in the T cells from pat ients with CTCL because enhanced proliferation relative to anti-TCR/CD 3 or mitogenic lectins was found when anti-CD2 or anti-CD28 plus phorb ol ester was used as stimulant. Despite the brisk proliferation induce d by anti-CDw60, anti-CD2, or anti-CD28, T cells from the patients did not produce detectable amounts of gamma-interferon. The inability to produce gamma-interferon correlates with our finding of absent (n = 3) or weak (n = 1) intercellular adhesion molecule-1 expression in the l esional keratinocytes in these patients. In conclusion, T cells of pat ients with CTCL demonstrate elevated expression of a T-cell-independen t signaling molecule CDw60 and respond to antigen-independent activati ng signals.