The T-cell CD2 determinant mediates inhibition of erythropoiesis by the
lymphokine cascade
S Burdach, M Shatsky, B Wagenhorst and L Levitt
Division of Hematology, Stanford University Medical Center, CA 94305.
We examined the role of the T-cell antigen CD2 in the regulation of
erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2)
receptors (p55) were induced via triggering of the antigen receptor-
associated CD3 epitope. Before CD3 triggering T cells were preincubated
with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets
were employed during incubation to facilitate interaction between T-cell
LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55
expression after three to six days of culture with IL- 2. Next we assessed
the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2
blockade on IL-2-induced inhibition of BFU-E in autologous cocultures
containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition
(52% to 92%) of BFU-E in the presence but not in the absence of
CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a
65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2)
U/mL IL-2. Preincubation of CD3- triggered T cells with isotype control
antibody had no effect on IL-2- induced erythroid inhibition. Day 3
supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T
cells established in the presence of IL-2 were next assessed for modulation
of BFU-E. CD3-triggered T- cell supernatants caused a 77% +/- 9% inhibition
of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E
inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma)
release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of
culture. In control experiments, the addition of IF gamma-neutralizing
monoclonal antibody to CD3-triggered T-cell supernatant established in the
presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We
conclude that blockade of the CD2 T-cell determinant induces down
modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced
inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release.
These data suggest that the T-cell CD2 determinant can exert a regulatory
effect on the control of erythropoiesis by the lymphokine cascade.
Volume 72,
Issue 2,
pp. 770-775,
08/01/1988
Copyright © 1988 by The American Society of Hematology
