Protection of xenografts by a combination of immunoisolation and a single dose of anti-CD4 antibody

Immunoisolation is the separation of transplanted cells from cells of the i mmune system using a semipermeable membrane. Using one such immunoisolation capsule-the TheraCyte (R) device-we have assessed the survival of encapsul ated xenogeneic tissue in vivo as well as the contribution of CD3(+\e) T ce lls to encapsulated xenograft rejection. The foreign body reaction to the T heraCyte (R) capsule in vivo was assessed by transplanting empty capsules i nto normal mice. These capsules elicit a foreign body response by the host animal. Encapsulated CHO, NIT-1, and PK-15 cells were placed in culture and in immunodeficient mice to investigate their growth characteristics in the TheraCyte (R) device. These cell lines survive both in culture and in immu nodeficient SCID mice. Xenogeneic PK cells were also transplanted into norm al C57BL/6 mice. These cells do not survive in normal mice despite the abse nce of direct contact between infiltrating and encapsulated cells. In addit ion, the survival of encapsulated cells in mice treated with a single dose of anti-CD4 antibody was examined. This was assessed using two systems: 1) histological analysis of capsule sections: 2) a quantitative luciferase rep orter system using PK cells transfected to express luciferase. In both case s, anti-CD4 antibody contributed to prolonged encapsulated xenogeneic cell survival. Encapsulated xenogeneic cells survive in immunodeficient mice but not normal mice. Treatment of normal mice with anti-CD3 antibody results i n prolonged survival of xenogeneic cells that can be measured using a lucif erase reporter system. These results highlight the contribution of CD4(+\e) T cells to encapsulated xenograft rejection.