Reversion of the SCID phenotype by human T cell grafts. Development of cross-species immunocompetence
Donjon, C.M.; Morkowski, H.; Cheung, R.K.; Leeder, J.S.; Dosch, H.M.
Journal of Immunology 151(11): 5948-5954
1993
ISSN/ISBN: 0022-1767 PMID: 8245439 Document Number: 417325
Due to defective recombinase function, mice with severe combined immunodeficiency (SCID) lack functional lymphocytes and can accept human lymphoid xenografts. Xenografted animals (SCID-hum) are thought to provide a neutral environment for in vivo studies of normal, malignant or HIV-infected human cells. SCID-hum often develop endogenous, EBV+ lymphomas in the graft and in the our study two-thirds of 142 SCID-hum 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.