Enhanced Engraftment of HTLV‐I‐Infected Human T Cells in Severe Combined Immunodeficiency Mice by Anti‐asialo GM‐1 Antibody Treatment

Abstract

The effects of anti‐asialo GM‐1 antibody (AAGM) treatment on the engraftment of human T‐cell leukemia virus type I (HTLV‐I)‐infected human T cells in severe combined immunodeficiency (SCID) mice were studied. The frequency of tumor formation in an HTLV‐I‐transformed human T‐cell line, MT‐2 cells, at the site of inoculation was significantly higher in AAGM‐treated than untreated mice (P<0.05): 16/18 (89%) and 16/26 (62%), respectively. The promotive effect of AAGM treatment on tumor development was marked in the early stage (less than 3 weeks), suggesting that the immediate reaction of natural killers to the inoculated cells may be important for the prevention of tumor development. The surface phenotypes and clonality of the tumor cells were the same as the MT‐2 cells inoculated. Inoculation of peripheral blood mononuclear cells (PBMC) from one of the 4 adult T‐cell leukemia/lymphoma (ATL) patients resulted in the development of tumors in AAGM‐treated SCID mice. However, the surface phenotypes of the cells from these tumors were a mixture of B cells and T cells, suggesting that these tumors consisted of Epstein‐Barr virus‐transformed B cells and HTLV‐I‐transformed T cells. In addition, HTLV‐I was detected by polymerase chain reaction in various organs of the mice inoculated with PBMC from the ATL patient and the asymptomatic carrier examined. These results suggest that elimination of natural killer function by AAGM treatment is important, although such treatment is not always necessary for the engraftment of HTLV‐I‐infected cells in SCID mice.

Enhanced Tumor Growth and Invasiveness in Vivo by a Carboxyl-Terminal Fragment of α1-Proteinase Inhibitor Generated by Matrix Metalloproteinases

“…23 In nude mice, NK-cell-mediated control of tumor growth is an important defense mechanism against the tumor, and in fact, anti-asialo GM-1 treatment enhances the growth of tumor cells in nude mice. 23,24 When 5 ϫ 10 5 cells (1/10 of the first experiment) were injected subcu- Figure 3. Construction of ␣PI-C expression/secretion vector (pCI-neoATIM) and selection of ␣PI-C secreting clones.…”