A rat monoclonal anti-(human CD2) and L-leucine methyl ester impacts on human/SCID mouse graft and B lymphoproliferative syndrome.
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.
Bombil
F
F
Experimental Immunology Unit, University of Louvain, Brussels, Belgium.
Kints
J P
JP
Havaux
X
X
Scheiff
J M
JM
Bazin
H
H
Latinne
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D016913:Blood Component Transfusion; D018801:CD2 Antigens / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; C105249:LO-CD2a; C030365:leucine methyl ester; D007930:Leucine