Engraftment and activity of anti-CD3-activated human peripheral blood lymphocytes transferred into mice with severe combined immune deficiency.
Human PBL (huPBL) were activated with anti-CD3 mAb in vitro and then were transferred into mice with severe combined immune deficiency (SCID) to determine the effect of activation on engraftment and to determine if the engrafted human cells could provide antitumor effects in mice. Some mice were also treated with human rIL-2 after huPBL transfer. Mice were analyzed 6 to 8 wk after cell transfer and the number of human cells in the peripheral lymphoid organs was determined. Mice receiving anti-CD3-activated huPBL demonstrated a significant increase in the incidence of human T cell engraftment in the periphery as assessed by flow cytometry. Human cells were also detected in the murine thymus after anti-CD3 stimulation indicating that human T cells can migrate to the murine thymus provided that they are activated before the transfer. The transfer of anti-CD3-activated huPBL also resulted in an xenogeneic graft-vs-host reaction manifested primarily by proliferation of murine splenic hemopoietic cells. When SCID mice received the human colon carcinoma HT29, the concurrent transfer of anti-CD3-activated human cells resulted in a significant increase in survival. However, the human cells displayed low cytolytic activity toward human tumor targets when they were recovered from the lymphoid organs of the SCID recipients. Supernatants from the anti-CD3-activated cells were able to inhibit the growth of HT29 in vitro, partly because of the presence of IFN-gamma, suggesting that the human T cells are producing cytokines in vivo that have antitumor effects. Thus, the use of anti-CD3-activated huPBL in SCID mice may be of value for optimizing human cell engraftment in the human/mouse lymphoid chimeras and may be used to evaluate potential anti-neoplastic therapies that employ human effector cells.
Murphy
W J
WJ
Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Conlon
K C
KC
Sayers
T J
TJ
Wiltrout
R H
RH
Back
T C
TC
Ortaldo
J R
JR
Longo
D L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002678:Chimera; D003602:Cytotoxicity, Immunologic; D006087:Graft vs Host Reaction; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D011994:Recombinant Proteins