Defective interleukin-2 production and responsiveness by T cells in
patients with chronic lymphocytic leukemia of B cell variety
O Ayanlar-Batuman, E Ebert and SP Hauptman
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.
Volume 67,
Issue 2,
pp. 279-284,
02/01/1986
Copyright © 1986 by The American Society of Hematology
