Reduction of lethal graft-versus-host disease: transplantation of cultured XXXX bone marrow across minor histocompatibility differences.

@entity19 @entity236 @entity2132
The @entity19 bone marrow culture technique was used to prepare donor marrow for @entity236 minor histocompatibility complex differences. Previous studies have shown that theta-positive cells are rapidly lost from such cultures and that transplantation of cultured marrow across major histocompatibility complex differences results in a delay in the development of lethal @entity2132 ( @entity2132 ). In this study, a total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming units]) from three-day-old cultures were used as a source of donor marrow. Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into CBA/J; and C57BL/6 into LP/J. Donor @entity19 were immunized with recipient spleen cells prior to culture in order to increase the graft-v-host response. For LP/J marrow into C57BL/6 @entity19 , 5 X 10(7) donor spleen cells transplanted along with the marrow were needed to induce lethal @entity2132 . However, lethal @entity2132 was seen without the addition of spleen cells for BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals receiving fresh marrow were dead of @entity2132 five weeks after transplantation. With the use of cultured marrow the three-month survival was 80%, 51%, and 93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6 into LP/J strain combinations. Long-term donor engraftment in all recipient animals receiving cultured marrow was confirmed by analyzing hemoglobin polymorphisms between the strain combinations. These results demonstrate that in contrast to transplantation across major histocompatibility complex differences, the use of cultured cells for @entity236 minor histocompatibility complex differences allows for engraftment while reducing the risk of lethal @entity2132 .
