Defective spontaneous and antibody-dependent cytotoxicity mediated by E-rosette-positive and E-rosette-negative cells in untreated patientswith chronic lymphocytic leukemia: Augmentation by in vitro treatment with interferon

Peripheral blood E-rosette-positive and E-rosette-negative lymphocytes from 12 untreated patients with chronic lymphocytic leukemia (CLL) were separated by rosetting with neuraminidase-trated sheep erythrocytes and examined for spontaneous (SLMC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Four of 12 patients examined had normal T cell ADCC, and two patients exhibited normal levels of T cell SLMC. All patients exhibited defective spontaneous and antibody-dependent cytotoxicity mediated by the E-rosette-negative population even at considerably high effector-to-target ratios. Cells isolated from the E-rosette-negative population by rosetting with Ripley serum-coated human erythrocytes also lack spontaneous lymphocyte-mediated cytotoxicity. In vitro treatment of the E-rosette-positive and E-rosette-negative cells from these patients with human leukocyte interferon significantly increased (P < 0.005 or P < 0.001) to normal or subnormal levels the T cell SLMC in eight of 12 patients but failed to increase the SLMC and ADCC mediated by the E-rosette-negative population. A significant (P < 0.001) augmentation of the T cell SLMC by treatment in vitro with interferon was observed in the majority of normal donors. Statistically significant increase by in vitro interferon treatment of the T cell ADCC was observed in five of 12 patients. A significant (P < 0.001) augmentation of the T cell ADCC by in vitro interferon treatment was also observed in 30% of the normal donors examined. Simultaneous analysis of the proportions of the peripheral blood T cell subsets, as defined by Fc receptors, in these patients revealed a marked imbalance of the Tμ and Tγ cells. Although the proportions of the Tμ cells were found to be normal, a marked increase was observed in the proportion of the Tγ cells. Furthermore, significant numbers of cells bearing Fc receptors for both IgM and IgG (Tμγ cells) were observed by a double rosetting technique, in certain patients. In vitro treatment of T lymphocytes with human leukocyte interferon did not alter the proportions of T cells with Fc receptors for IgM or IgG in any of the patients or the normal donors, including those where SLMC or ADCC were augmented. These studies demonstrate that a) spontaneous and antibody-dependent cytotoxicity mediated by E-rosette-positive and E-rosette-negative cells are regularly impaired in patients with CLL; b) in vitro interferon treatment restored the T cell SLMC and ADCC in certain patients, whereas this treatment was completely ineffective in restoring the non-T cell SLMC or ADCC; and c) a marked imbalance of the proportion of the Tμ and Tγ cells as well as T cells bearing receptors for both IgM and IgG (Tμγ cells) are present in patients with CLL.