Mononuclear cells infiltrating kidney allografts in the absence of rejection Effect of conversion from cyclosporin to azathioprine therapy

Abstract

Focal small mononuclear cell infiltrates were found in renal allograft biopsies of 13/14 transplant recipients with a stable function after long-term cyclosporin A (CsA) therapy. Phenotypical analysis of the infiltrating cells using monoclonal antibodies showed a slight preponderance of T cells (56% +/- 8%), with only small percentages of B cells (5% +/- 2%), NK cells (2% +/- 1%), and monocytes (2% +/- 1%). Within the T-cell population the median calculated CD4/CD8 ratio was 1:3. Thirty-five percent of the infiltrating mononuclear cells remained unidentified with the monoclonal antibody panel used (silent cells). Three months after immunosuppressive therapy had been changed from CsA to azathioprine (AZA), the size of the infiltrates was significantly increased and there was a marked invasion of mononuclear cells between tubular epithelium despite a significant improvement in creatinine clearance (P less than 0.01). the phenotypical composition of these infiltrates was dominated by T cells (84% +/- 3%), with a median CD4/CD8 ratio of 2:7 due to an increase in CD4+ cells and a decrease in CD8+ after conversion (P less than 0.05). The percentages of B cells, NK cells, and monocytes showed no significant changes after conversion. During AZA therapy nearly all infiltrating mononuclear cells were stained with the monoclonals used, leaving no silent cells postconversion.

Intragraft cytokine expressionf in tolerant rat renal allografts with rapamycin and cyclosporin immunosuppression

“…These findings are not entirely unexpected. The data in the human literature correlate well with this (2,8), and many other models of animal transplantation also demonstrate mononuclear cells in significant density residing in normally functioning allografts (3,8). The role of these lymphocytes has been an area of much speculation (2,3).…”

“…The rejection of allotransplanted organs is mediated predominantly by host T-cells that are specifically activated by donor alloantigen. Activated T-lymphocytes are required for acute cell-mediated allograft rejection (ACR) (1), but allospecific cytotoxic T-cells can reside within an allograft without causing rejection (2,3). In rodent models where short-term immunosuppressive treatments can induce long-term tolerance, mononuclear cells have been observed in non-rejecting grafts before the establishment of alloantigen specific tolerance (3).…”

Key driver genes as potential therapeutic targets in renal allograft rejection

“…immune cell burden observed in TCMR (47). Consistent with the chemokine and cytokine transcript expression results, the immunohistochemistry staining ( Figure 7E) and quantification demonstrated reduced cell infiltrates in the minocycline-treated allografts, with significantly fewer CD3 + T cells (P = 0.001) and galectin-3-expressing macrophages (P = 0.0003) present compared with those that received saline.…”

The Immunologic Role of IFN-γ in ACI to Lewis Kidney Transplantation

“…The rejection of transplanted organs is mediated predominantly by host T-cells that are specifically activated by donor alloantigen. Activated T-lymphocytes are required for acute cell-mediated allograft rejection [1], but allospecific cytotoxic T-cells can reside within an allograft without causing rejection [2,3]. In rodent models where short-term immunosuppressive treatments can induce long-term tolerance, mononuclear cells have been observed in nonrejecting grafts before the establishment of alloantigen-specific tolerance [3].…”