Abnormal T lymphocyte subpopulations in patients with B cell chronic lymphocytic leukemia: an analysis by monoclonal antibodies.

Abstract

Human T lymphocyte subpopulations have been recently defined by monoclonal antibodies recognizing cell surface differentiation antigens selectively expressed on functionally distinct T cell subsets. The majority (93.27 f 4.67%) of the peripheral blood E rosette-forming cells are stained by the OKT3 monoclonal antibody. Helper (inducer) cells are OKT4 positive (64.87 f 7.39%), whereas cytotoxic/suppressor cells carry the OKT8 anti-gen (34.73 f 4.74%). We determined the proportions of T lymphocyte subpopulations as defined by monoclonal antibodies in 30 untreated patients with B cell chronic lymphocytic leukemia (CLL). These determinations were performed on purified E rosette-positive cells, and the results were expressed as the percent of the E rosetting cells. Patients with CLL exhibited in the peripheral blood decreased proportions of the T3-positive cells (80.53 f 17.02%; p e 0.007), significantly decreased proportions of T4-positive cells (50.83 f 14.33%; p e 0.0005), and significantly increased proportions of T8-positive cells (48.93 f 16.46%; p < 0.001). These imbalances of T lymphocyte subpopulations resulted in significantly decreased values (p-= 0.0005) of the ratio of the T4/T8 phenotypes in these patients (1.06 f 0.35 vs 1.93 f 0.26 of the normal controls). Only five of 30 patients studied exhibited abnormal proportions of both T4-positive and T8-positive cells, suggesting that two distinct types of T cell defects may be present in patients with CLL. Furthermore, significant proportions of cells carrying both these antigens were observed in certain patients with CLL, as determined by a double-labeling immunoflu-orescence method. Because of the increased absolute numbers of E rosette-forming cells in patients with B cell CLL, the numbers of T3-, T4-, and Ts-positive cells were found to be significantly increased (p < 0.0005) in these patients when compared with those of the normal controls. In vitro treatment of purified E rosette-positive cells from patients with CLL with thymopoietin pentapeptide (TP-5) significantly increased the T4/T8 ratio in seven of 15 patients studied. Simultaneous determinations of serum immunoglobulins G, A, and M revealed a significant correlation (p < 0.005) between the T4/T8 ratio and serum immunoglobulin G and A levels but not M. These results demonstrate a profound imbalance of T lymphocyte sub-populations, as defined by monoclonal antibodies, in patients with B cell chronic lymphocytic leukemia, and provide evidence suggesting an association of the ratio