Peripheral blood lymphocytes of nonleukemic lymphoma patients exhibit aberrant expression of T-cell activation markers after polyclonal stimulation in vitro

Abstract

The authors evaluated suppressed in vitro functions of peripheral blood lymphocytes (PBL) as a possible tool in the early diagnosis of human lymphoma. In 13 of 22 patients with recent onset of various types of nonleukemic lymphomas (Mb. Hodgkin and non-Hodgkin's lymphomas of B-cell and T-cell origin) the mitogen response of PBL against phytohemagglutinin (PHA) and concanavalin A (Con A), as measured by 3H-thymidine (3HTdR) uptake, was found to be significantly suppressed, whereas the response to pokeweed mitogen (PWM) was normal in 18 cases. In parallel, cytofluorimetric analysis was done with PBL after 72 hours in culture with and without PHA, using antibodies against the differentiation antigens: CD3, CD8, CD4, CD19, and CDw14 and the activation antigens: interleukin-2 (IL-2) receptor (IL-2R, CD25), human leukocyte antigen DR (HLA-DR), and transferrin receptor (TR). Compared with healthy controls and patients with other diseases, a significant reduction of the total T-cell blast response, i.e., the percentage of large T-cells bearing activation markers, was found in all lymphoma cases including those with a normal 3HTdR uptake. Furthermore, a pronounced inhibition in the expression of the activation markers Il-2R and TR, but not of HLA-DR, was detected on CD3+ cells in PHA-stimulated PBL of all lymphoma cases. Thus, polyclonal activation combined with activation antigens seems to give more accurate information about the functional defect(s) of PBL in an early state of lymphoma; these parameters may therefore be valuable diagnostically. The abnormal pattern in the expression of T-cell activation antigens after polyclonal stimulation may help in the understanding the cellular immune defects associated with lymphoma.