Receptor-specific inhibition of bone marrow erythropoiesis by recombinant
DNA-derived interleukin-2
SE Burdach and LJ Levitt
Interleukin-2 (IL-2) induces differential secretion of lymphokines by IL-2
receptor (IL-2R)-positive and IL-2R-negative T cells. We studied T cell
IL-2R-specific modulation of adult bone marrow erythropoiesis by
recombinant IL-2 (rIL-2). I3-2R were induced by CD3 T cell surface
determinant-triggering and analyzed by cytofluorography. Bone marrow
monocyte and T cell-depleted (NAB-T) target cells were assessed for early
erythroid progenitor expression (BFU-E) in the presence of 0 to 10(3) U/mL
of rIL-2, rIL-2 had no significant effect on BFU-E expression in the
absence of T cells or in the presence of IL-2R- negative T cells. rIL-2
caused a dose-dependent inhibition (75% to 90%) of BFU-E in the presence of
autologous IL-2R-positive T cells. The addition of anti-IL2-receptor
antibody to cultures containing rIL-2 plus IL-2R-positive T cells entirely
abrogated rIL-2-mediated inhibition of BFU-E. In the presence of rIL-2
(10(2) U/mL) production of interferon gamma (IF-gamma) by adult marrow
CD3-triggered IL-2R- positive T cells was increased 37- to 125-fold
compared to IL-2R- negative T cells. rIF-gamma caused a dose-dependent (88%
+/- 17% at 10(3) U/mL) inhibition of adult BFU-E in the presence of
CD3-triggered autologous T cells. rIL2-mediated inhibition of adult BFU-E
in the presence of IL-2R-positive T cells was partially abrogated (52% +/-
16%) following addition of monospecific IF-gamma antibody. These results
demonstrate (a) rIL-2 modulation of adult marrow erythropoiesis is
selectively dependent upon both the presence or absence of autologous T
cells and the IL-2R status of these T cells; and (b) rIL-2- induced
inhibition of adult marrow erythropoiesis is mediated in part by release of
IF-gamma from IL-2R-positive T cells.
Volume 69,
Issue 5,
pp. 1368-1375,
05/01/1987
Copyright © 1987 by The American Society of Hematology
