REDUCED SURFACE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR-TYPE-II IN MITOGEN-ACTIVATED T-CELLS FROM SEZARY PATIENTS

Sezary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4(+) T cells and immune dysfunctions, raising the possibility of cytokine-related abnormaliti es, We previously described a decreased response to the growth-inhibit ory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta recep tor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we devel oped a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4(+) T cells, Our results indicat e that unlike normal CD4(+) T cells, CD4(+) T cells from 9 of 12 SzS p atients expressed little, if any, surface TGF beta RII in response to mitogen stimulation, At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4(+) T cells, This indi cates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease.