EFFECT OF HUMAN CORD-BLOOD TRANSFER ON SURVIVAL AND DISEASE-ACTIVITY IN MRL-LPR/LPR MICE

The MRL-lpr/lpr mice have a genetic defect and by 6 months of age usually die after developing severe autoimmune disease and massively enlarged lymph nodes (Cohen, P. L., and Eisenberg, R.A., Annu. Rev. Immunol. 9, 243-269, 1991). Similarly as in some genetic diseases in humans, these mice, if given an appropriate marrow transplant from a mouse not having the defect, will have partial correction of the disease process and an extension of life (Cohen, P. L., and Eisenberg, R. A., Annu. Rev. Immunol. 9, 243-269, 1991; Lenarsky, C., Kohn, D. B., Weinberg, K. I., and Parkman, R, Hematol. Oncol. Clin. N. Am, 4, 589-603, 1990). Utilizing human umbilical cord blood as a donor source for marrow transplantation, we have been able to obtain significant correction of the MRL-lpr/lpr genetic defect and double the life span. By 11 months of age, 5 months beyond their usual life span, both the animals receiving congenic marrow (MRL-+/+) and the animals with human cord blood had mild lymphadenopathy, a decrease in double-positive T cells, and an increase in double-negative T cells. Granulomatous vasculitis could be identified in the animals receiving human cells and could not be found in the animals receiving MRL-+/+ marrow. (C) l995 Academic Press, Inc.