Defective Interleukin-2 Production and Responsiveness by T Cells in Patients With Chronic Lymphocytic Leukemia of B Cell Variety

• Published in: Blood 1986-02, Vol.67 (2), p.279-284
• Main Authors: Ayanlar-Batuman, Olcay, Ebert, Ellen, Hauptman, Stephen P.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal; B-Lymphocytes - physiology; Biological and medical sciences; Hematologic and hematopoietic diseases; Humans; In Vitro Techniques; Interleukin-2 - biosynthesis; Leukemia, Lymphoid - physiopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Medical sciences; Receptors, Antigen, B-Cell - analysis; Receptors, Immunologic - biosynthesis; Receptors, Interleukin-2; Rosette Formation; T-Lymphocytes - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V67.2.279.279

The present studies were designed to investigate the mechanism(s) of the defective T cell proliferative response to various stimuli in patients with B cell chronic lymphocytic leukemia B-CLL. In 14 patients with advanced B-CLL (stage III or IV) we found the T cell response in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) to be 35.7% and 30% of the controls, respectively. Proliferation in the MLR depends upon the production of and response to interleukin 2 (IL 2). a T cell growth factor. IL 2 production in eight B-CLL patients was 22% of the control. The response to IL 2 was measured by the increase in the T cell proliferation in the MLR with the addition of IL 2. T cell proliferation in both the auto and allo MLR of CLL patients was significantly lower than in the controls after the addition of IL 2. The proliferative response of normal T cells to stimulation by CLL B cells was 50% of the control. This latter response was increased to control levels when cultures were supplemented with exogenous IL 2. suggesting that CLL B cells could stimulate IL 2 receptor generation in normal T cells in an allo MLR, but not IL 2 production. The presence of IL 2 receptors on activated T cells was directly determined using anti-Tac, a monoclonal antibody with specificity for the IL 2 receptor. Of the mitogen- or MLR-activated T cells in CLL patients, 6% and 10%, respectively, expressed Tac antigen, whereas identically stimulated control T cells were 60% and 47% Tac +, respectively. Our findings suggest that T cells in B-CLL are defective in their recognition of self or foreign major histocompatibility antigens as demonstrated by their impaired responsiveness in the MLR. Thus, these cells are unable to produce IL 2 or generate IL 2 receptors. © 1986 by Grune & Stratton, Inc.