Survival and tissue distribution of human T-cell clones in SCID mice.

Abstract

Evidence from animal experiments and clinical trials suggests that in vitro expanded T-cell clones could be useful in adoptive therapy of cancer and viral infections. To establish an in vivo model for adoptive therapy with cloned human T cells, we studied the survival and tissue distribution of human αβ CD4 + T-cell clones transplanted intraperitoneally into mice with severe combined immune deficiency (SCID) mice. Four clones, expanded in vitro in recombinant human interleukin-2 (IL-2), were injected into 14 cyclophosphamide-conditioned mice, subsequently inoculated daily with IL-2. Using flow-cytometry analysis, human T cells were detected in the peritoneal cavity wash (PCW) but not in other tissues of 12 mice at 1 to 4 weeks after injection. A reverse transcriptase polymerase chain reaction (RT-PCR) specific for the constant region of human TCR β chain revealed a positive signal in 12 of 14 mice in PCW, eight in spleen, seven in lymph nodes, seven in liver, six in bone marrow, and two in blood. The frequency of human T-cell detection decreased with time. Five to seven sites were positive in mice killed at 1 week, one to four sites at 2 weeks, none to one site at 3 weeks, and three sites at four weeks. Thus human T-cell clones transplanted in SCID mice can survive for at least 4 weeks, even in the absence of specific antigen. The clones migrate at low levels outside the peritoneal cavity ; therefore, the SCID mouse might serve as a model to study adoptive therapy with cloned T cells.