Abnormal T cell function in early-stage chronic lymphocytic leukemia (CLL) patients

Abstract

Significant alterations in T cell subpopulations and function occur in chronic lymphocytic leukemia (CLL) patients. We studied whether abnormalities in peripheral blood T cell parameters were present in 15 untreated early stage CLL patients (ie, Rai stage 0, 1, 2). Seven of the nine patients showed decreased T helper support as compared to control T cells for pokeweed mitogen (PWM)-induced control B cell proliferation (ie, patient 6,063 +/- 1,434 cpm vs control 14,894 +/- 121 cpm). All stage 0 and 1 patients showed a marked impairment of T helper activity for control B cell proliferation (patient T = 7,752 +/- 1,137 cpm vs control T = 14,894 +/- 121 cpm). In a separate assay system, six of nine CLL patients showed T suppressor activity for control B cell proliferation greater than control T cell suppressor activity. Four patients were stage 0 and 1. CLL patients demonstrated markedly impaired T cell support for control B cell immunoglobulin synthesis compared to control T cells (188 +/- 28 vs 869 +/- 56 hemolytic plaque-forming cells (HePFC)/culture, respectively). Control T cells showed increasing support for control B cell immunoglobulin synthesis with increasing T:B cell ratios (869 +/- 56 vs 1,265 +/- 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). In contrast, five of eight CLL patients' T cells showed no improvement in control B cell immunoglobulin synthesis with increasing T:B cell ratios (795 +/- 56 vs 569 +/- 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). There was no direct correlation with CLL T cell-mediated suppression of B cell proliferation and suppression of B cell immunoglobulin synthesis. These studies suggest there is a complex array of abnormal immunoregulatory T cell function in early stage CLL. These include a prominent T helper dysfunction and more variable excessive suppressor activity. The relationship of these findings to the basic disease process remains to be elucidated.