Ch. Uittenbogaart et al., THE SCID MOUSE ENVIRONMENT CAUSES IMMUNOPHENOTYPIC CHANGES IN HUMAN IMMATURE T-CELL LINES, International journal of cancer, 56(4), 1994, pp. 546-551
In order to evaluate whether the SCID mouse can provide the microenvir
onment for the growth of human immature T-cell leukemias and if in viv
o growth alters their phenotype, we examined the behavior of 3 weft-ch
aracterized T-cell acute lymphoblastic leukemia CT-ALL)-derived T-ceIl
lines which are at different stages of maturation (CEM, SUP-T3 and MO
LT-4f) after transfer to non-irradiated SCID mice. All 3 T-cell lines
engrafted and proliferated to form tumors in the mice and showed disse
mination patterns in the SCID mouse comparable to those of T-ALL in ma
n: i.e., human cells were detectable by flow cytometry or were culture
d from mouse bone marrow, spleen, liver or thymus. CEM, which is the m
ost immature T-cell line, readily formed tumors after injection of cel
ls. The more mature T-cell lines, SUP-T3 and MOLT-4f, required a longe
r time period, even after injection of higher cell numbers, Whereas no
changes in the configuration of the rearranged T-cell receptor genes
were detected, striking phenotypic changes were observed in all 3 leuk
emias growing in the SCID mice after injection. SCID-CEM cells showed
an increase in the surface expression of CD3 and CD8 and a decrease in
the expression of CD1 and CD71 (transferrin-receptor). SCID-MOLT-4f c
ells showed an increase in CD5 and CD8 expression and a decrease in CD
45RA expression. SCID-SUP-T3 cells showed increased expression of CD8
and CD45RA. Apparently, the mouse environment caused changes in cell-s
urface antigen expression on the T-ALL-derived T-cell lines. Some immu
nophenotypic changes remained stable during subsequent growth in cultu
re of SUP-T3 cells, suggesting that maturation of the cell line occurr
ed in vivo. The other cell lines, CEM and MOLT-4f after undergoing in
vivo-induced changes, reverted to the original immunophenotype, sugges
ting transitory activation in vivo. These data point out the importanc
e of stromal factors in defining growth and maturation of human leukem
ic cells in vivo, in SCID mice. (C) 1994 Wiley-Liss, Inc.