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 increases of CD57+ and CD28- cells among both circulating CD4+ and CD8+ 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 detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57+/CD28- T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-gamma, and TNF-alpha than their CD57-/CD28+ counterparts. Cytotoxic activity of circulating CD8+ T lymphocytes, measured ex vivo 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. Finally, the patients' CD57+/CD28- T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57+/CD28- T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.
Laboratory of Experimental Immunology, Faculty of Medicine, Catholic University of Leuven, Belgium.
L E
LE
Van den Hove
S W
SW
Van Gool
P
P
Vandenberghe
M A
MA
Boogaerts
J L
JL
Ceuppens
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D017209:Apoptosis; D018106:CD28 Antigens / Q000032:analysis*; D018959:CD57 Antigens / Q000032:analysis*; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000276:immunology; D008223:Lymphoma / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology; D010265:Paraproteinemias / Q000097:blood / Q000276:immunology; D012016:Reference Values; D012044:Regression Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
D015703:Antigens, CD; D018106:CD28 Antigens; D018959:CD57 Antigens