Natural Antibodies and Alloreactive T Cells Long after Kidney Transplantation

<p><strong>BACKGROUND: </strong>The relationship between circulating effector memory T and B cells long after transplantation and their susceptibility to immunosuppression are unknown. To investigate the impact of antirejection therapy on T cell-B cell coordinated immune responses, we assessed IFN-<em>γ</em>-producing memory cells and natural antibodies (nAbs) that potentially bind to autoantigens on the graft.</p><p><strong>METHODS: </strong>Plasma levels of IgG nAbs to malondialdehyde (MDA) were measured in 145 kidney transplant recipients at 5-7 years after transplantation. In 54 of these patients, the number of donor-reactive IFN-<em>γ</em>-producing cells was determined. 35/145 patients experienced rejection, 18 of which occurred within 1 year after transplantation.</p><p><strong>RESULTS: </strong>The number of donor-reactive IFN-<em>γ</em>-producing cells and the levels of nAbs were comparable between rejectors and nonrejectors. The nAbs levels were positively correlated with the number of donor-reactive IFN-<em>γ</em>-producing cells (<em>r</em> _s = 0.39, <em>p</em>=0.004). The positive correlation was only observed in rejectors (<em>r</em> _s = 0.53, <em>p</em>=0.003; nonrejectors: <em>r</em> _s = 0.24, <em>p</em>=0.23). Moreover, we observed that intravenous immune globulin treatment affected the level of nAbs and this effect was found in patients who experienced a late ca-ABMR compared to nonrejectors (<em>p</em>=0.008).</p><p><strong>CONCLUSION: </strong>The positive correlation found between alloreactive T cells and nAbs in rejectors suggests an intricate role for both components of the immune response in the rejection process. Treatment with intravenous immune globulin impacted nAbs.</p>