The effect of a depleting anti-CD4 monoclonal antibody on T cells and fetal pig islet xenograft survival in various strains of mice.

The effect of a cell-depleting anti-CD4 monoclonal antibody (mAb), GK1.5, was studied in a number of strains of inbred mice. Young adult female NOD/Lt, CBA and BALB/c mice were transplanted with organ cultured fetal pig pancreas and given 0.3 mg of the mAb (as ascites) on days -1, 0 and +1. The grafts were mostly rejected within 13 days in CBA mice but BALB/c and NOD recipients still had essentially intact grafts with the NOD mice showing evidence of early rejection. By 28 days posttransplantation the BALB/c recipients still had well-preserved grafts with minimal infiltration, but NOD and CBA mice had generally rejected their grafts totally. Peritransplant mAb treatment reduced CD4+ T cells in the spleen and they showed only incomplete recovery by 28 days. To further analyse the effect of anti-CD4 treatment, these strains as well as C57BL/6 mice were given a single dose (0.3 mg) of GK1.5 either as ascites or as affinity purified mAb. There was no obvious difference in effect between the ascites and the purified mAb within a strain but the various strains showed consistent differences in their blood, spleen and lymph node lymphocytes and in their response to the mAb. C57BL/6 mice differed from the other strains in having fewer T cells but more B cells in the blood, spleen and lymph nodes and a low CD4/CD8 ratio. Recovery of CD4+ T cells was most rapid in NOD mice and this together with the relatively high number of these cells may account for the ability of these mice to reject grafts despite immunosuppression that can allow prolonged graft survival in other strains. This study emphasizes the need to examine various strains of mice when making general statements about the efficacy of immunosuppression in transplantation and stresses the need to be aware of the frequent use of 'permissive' strains in reports where excellent graft survival is reported.