Phenotypic changes induced by interleukin-2 (IL-2) and IL-3 in an immature
T-lymphocytic leukemia are associated with regulated expression of IL-2
receptor beta chain and of protein tyrosine kinases LCK and LYN
R O'Connor, T Torigoe, JC Reed and D Santoli
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
We have previously reported the establishment of an interleukin-3 (IL-
3)-dependent and phenotypically myeloid cell line (TALL-103/3), obtained by
culturing cells from an immature T-lymphoblastic leukemia in the presence
of IL-3. These cells differentiated into a T-lymphoid cell line
(TALL-103/2) upon removal of IL-3 and incubation in IL-2. Despite the
different phenotype, the two cell lines remained karyotypically and
genotypically identical. Here, we have analyzed the phenotypic changes and
the signaling events induced by these two lymphokines in TALL-103/3 cells
by switching them to temporary growth in IL-2 and returning them to IL-3.
All four sublines obtained (the myeloid in IL-3 and the lymphoid in IL-2)
expressed RNA for CD3, IL-2 receptor (R) alpha, and T-cell receptor
(TCR)-gamma and -delta chains. However, cells cultured in IL-3 failed to
express detectable levels of the IL-2R beta chain at both the protein and
RNA levels, whereas cells exposed to IL-2 always expressed IL-2R beta. In
parallel with the changes in IL-2R beta expression, the SRC-like protein
tyrosine kinase (PTK) p56 LCK could not be detected in IL-3-dependent
cells, but was abundant in the IL-2-dependent cells and underwent markedly
increased autophosphorylation in response to IL-2. In contrast, p53/p56 LYN
was highly expressed in IL-3-dependent cells, and greatly decreased when
these cells were switched to growth in IL-2. LYN kinase autophosphorylation
modestly increased in response to IL-3. None of the other kinases in the
SRC family that were tested underwent increased autophosphorylation after
lymphokine stimulation, indicating the specificity of IL-2 for LCK and of
IL-3 for LYN. The TALL-103 cell lines provide a unique system to study the
interaction between lymphokines and SRC-family PTKs in signal transduction
pathways leading to hematopoietic cell differentiation.
Volume 80,
Issue 4,
pp. 1017-1025,
08/15/1992
Copyright © 1992 by The American Society of Hematology