Reversion of the SCID phenotype by human T cell grafts. Development of cross-species immunocompetence.
Due to defective recombinase function, mice with severe combined immunodeficiency (SCID) lack functional lymphocytes and can accept human lymphoid xenografts. Xenografted animals (SCIDhum) are thought to provide a neutral environment for in vivo studies of normal, malignant or HIV-infected human cells. SCIDhum often develop endogenous, EBV+ lymphomas in the graft and in the our study two-thirds of 142 SCIDhum mice did so. Surprisingly, one-third of animals developed reversion of the SCID phenotype rapidly after human T cell engraftment. 90% of tumors occurred in nonrevertant and only 10% in revertant mice. These revertant animals showed immunologic tolerance for normal human B lymphocytes, maintained stable levels of mouse and human IgM and IgG. In addition, they generated competent mouse T cells able to kill transformed (EBV+) but not fresh B cells from the same donor nor unrelated human B cell lines. The tolerance for human lymphoid cells and the cross-species antitumor competence of host T lymphocytes imply unexpected recognition and selection events. Rather than a neutral "bioreactor," these observations mark the SCID host as potentially active participant in a composite immune system generated by xenografting.
Donjon
C M
CM
Department of Pediatrics, University of Toronto, Hospital For Sick Children, Ontario, Canada.
Morkowski
H
H
Cheung
R K
RK
Leeder
J S
JS
Dosch
H M
HM
D000818:Animals; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human; D006801:Humans; D007121:Immunocompetence; D008223:Lymphoma / Q000209:etiology* / Q000276:immunology; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014183:Transplantation, Heterologous; D014412:Tumor Virus Infections / Q000209:etiology* / Q000276:immunology