Immune mechanisms associated with the rejection of fetal murine proislet allografts and pig proislet xenografts: Comparison of intragraft cytokine mRNA profile

Background previous in vivo depletion studies of CD4 and CD8 T cells indica ted that different rejection mechanisms operate for proislet allografts and xenografts. The cellular and molecular mechanisms of acute proislet allogr aft and xenograft rejection have therefore been characterized and directly compared, Methods. The intragraft cytokine mRNA profile in rejecting BALB/c (H-2(d)) proislet allografts was analyzed in control, CD4 T cell-depleted, and CD8 T cell-depleted CBA/H (H-2(k)) recipient mice using semi-quantitative revers e transcriptase-assisted polymerase chain reaction (RT-PCR), The cytokine p rofiles for proislet allografts and pig proislet xenografts at 3-10 days po sttransplant were directly compared and correlated with graft histopatholog y, Results. Allograft rejection was protracted (2-3 weeks), characterized by i nfiltrating CD8 T cells and CD4 T cells (no eosinophils) and was associated with a Th1-type CD4 T cell response (IL-2, IFN-gamma, and IL-3 mRNA) and a CD8 T cell-dependent spectrum of cytokine gene expression (IL-2, IFN-gamma , IL-3, and IL-10 mRNA). Xenograft rejection was rapid (6-8 days), involved predominantly CD4 T cells and eosinophils, and in contrast to allografts, exhibited intragraft mRNA expression for the Th2 cytokines IL-4 and IL-5, Conclusions. Proislet allograft and xenograft rejection differ in the tempo of destruction, phenotype of the cellular response and intragraft profile of cytokine mRNA The recruitment of eosinophils only to the site of xeno-re jection correlates with IL-4 and IL-5 mRNA expression. These findings sugge st that different anti-rejection strategies may need to be developed to opt imally target the allograft and the xenograft response.