A rat monoclonal anti-(human CD2) andL-leucine methyl ester impacts on human/SCID mouse graft and B lymphoproliferative syndrome |
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Authors: | Fataki Bombil Jean Pierre Kints Xavier Havaux Jean Marie Scheiff Hervé Bazin Dominique Latinne |
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Institution: | (1) Experimental Immunology Unit, University of Louvain, Clos chapelle-aux-champs 30 – 56, Brussels 1200, Belgium, BE;(2) Laboratory of haematology and Histology, University of Louvain, St. Luc Hospital, Brussels, Belgium, BE;(3) Transplantation Immunology, University of Louvain, St. Luc Hospital, Brussels, Belgium, BE |
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Abstract: | The transfer of human peripheral blood mononuclear cells (hu-PBMC) from adult Epstein-Barr- virus(EBV)-seropositive donors
in SCID (severe combined immunodeficiency) mice frequently leads to the development of a human B lymphoproliferative syndrome
(hu-BLPS). Therefore, as 90% of adult potential donors are EBV-seropositive, efforts have to be made to avoid the occurrence
of this B lymphoproliferative disorder. McCune et al. Science 241:1632 (1988)] used human fetal organs for a human SCID graft.
This system does not give rise to hu-BLPS but human fetal organs are much less available than peripheral blood leucocytes.
The experiments reported in this paper show how crucial is the presence of functional T lymphocytes for a graft to take and for development of hu-BLPS in hu-PBMC-reconstituted SCID mice, since inhibition of
T lymphocyte by a rat anti-(human CD2) monoclonal antibody (LO-CD2a) during the first 10 days of the graft prevents successful
engraftment of human normal lymphocytes as well as hu-BLPS in SCID mice. The transfer of B cells alone or B cells plus monocytes
in SCID mice does not permit either long-term engraftment or development of hu-BLPS. We also demonstrate that hu-PBMC treated
with L-leucine methyl ester are less susceptible to the development of hu-BLPS after engraftment in SCID mice than are untreated
hu-PBMC. The mechanism of action of L-leucine methyl ester on these cells is discussed.
Received: 12 December 1994 / Accepted: 20 March 1995 |
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Keywords: | Human-SCID mice B lymphoproliferative syndrome T lymphocyte LO-CD2a L-Leucine methyl ester |
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