THE SCID MOUSE ENVIRONMENT CAUSES IMMUNOPHENOTYPIC CHANGES IN HUMAN IMMATURE T-CELL LINES

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.