CD57(+) CD28(-) T-CELLS IN UNTREATED HEMATO-ONCOLOGICAL PATIENTS ARE EXPANDED AND DISPLAY A TH1-TYPE CYTOKINE SECRETION PROFILE, EX-VIVO CYTOLYTIC ACTIVITY AND ENHANCED TENDENCY TO APOPTOSIS/

Three-color flow cytometry immunophenotyping revealed significant incr eases of CD57(+) and CD28(-) cells among both circulating CD4(+) and C D8(+) T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57(+) cells among circulating CD4(+) T lymphocytes was frequently d etected in patients with chronic leukemia of B cell origin (B-CLL, hai ry cell leukemia) but not in patients with chronic myeloid leukemia, s uggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation technique s, we further demonstrate that the patients' CD57(+)/CD28(-) T cells d isplay a typical Th1-type cytokine secretion profile upon anti-CD3 sti mulation, with a markedly higher secretion of the Th1-type cytokines I L-2, IFN-gamma, and TNF-alpha than their CD57(-)/CD28(+) counterparts. Cytotoxic activity of circulating CD8(+) T lymphocytes, measured ex v ivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57(+)/CD28(-) subset. Moreover, a marked cytotoxic activity was detected within CD4(+)CD57(+) T cells from some B-CLL patients. Final ly, the patients' CD57(+)/CD28(-) T cells displayed an increased tende ncy to apoptosis in culture. Collectively, our results indicate that t he expanded CD57(+)/CD28(-) T cells in hemato-oncological patients rep resent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.