Immunosuppression to cardiac allografts and soluble antigens by anti- XXXX and anti-very late antigen-4 monoclonal antibodies.

@entity1 @entity19 @entity5168 @entity12829 @entity6580
Effective activation of T cells in immune responses depends on two signals, one from the @entity5168 /TCR complex and another from accessory cell surface proteins. Very late Ag-4 (VLA-4) can exert a costimulatory function upon binding with @entity6580 ( @entity6580 ). We investigated the effects of mAbs against @entity6580 and VLA-4 on cardiac allograft survival and humoral response to soluble Ags. BALB/c hearts were transplanted into C3H/He recipients. mAbs (100 micrograms/day) were administered i.p. for the first 6 days. Graft survival in @entity19 treated with M/ @entity12829 (anti- @entity6580 ; median survival: 20 days, n = 6) and those treated with PS/2 (anti-VLA-4; 30 days, n = 6) was greater than that in control @entity19 (8 days, n = 7). Eight of 18 @entity19 treated with both M/ @entity12829 accepted the grafts over 65 days, and five of them accepted the grafts over 100 days. Allografts treated with the two mAbs showed scattered infiltration of leukocytes without evidence of active rejection at 65 days. @entity19 with long-surviving cardiac grafts were challenged with skin grafts from donor and third-party (C57BL/6) strains. Survival of the donor-type skin was significantly greater than that of the third-party skin. One @entity19 specifically accepted the donor-type skin indefinitely (> 150 days). FACS analysis of splenocytes at 55 days after transplantation showed complete recovery of VLA-4 expression from a down-regulation observed at day 7. In addition, @entity19 immunized with heat-aggregated @entity1 gamma-globulin did not produce specific Ab, even after boost immunization, if PS/2 was administered at the time of the first immunization. This unresponsiveness to xenogeneic protein lasted for more than 50 days. These results indicate that in vivo administration of anti- @entity6580 and anti-VLA-4 mAbs induces specific immunosuppression to cardiac allografts and soluble Ags.
