Abstract. The pathogenesis of chronic allograft nephropathy (CAN) involves both immunologic (antigen-dependent) and nonimmunologic (antigen-independent) mechanisms. In order to provide further insight into the immunologic basis of this disease, a cross-sectional analysis of cellular and humoral immunity in human renal allograft recipients with or without deteriorating renal function and biopsy proven CAN was performed. Interferon-␥ enzyme-linked immunosorbent spot assays were used to assess cellular immunity to donor, or fully mismatched third-party stimulator cells (direct pathway), and to synthetic peptides derived from donor HLA molecules (indirect pathway). Anti-HLA antibodies were evaluated by flow cytometry using HLA-coated beads. Both the mean frequencies of donor-reactive peripheral blood lymphocytes and the number of individuals who responded to donor antigens per group were statistically higher in CAN patients versus control subjects (P Ͻ 0.02). Calculated ratios of donor/third-party enzyme-linked immunosorbent spot responses showed mean values of 2.61 Ϯ 3.0 in the CAN group, with ratios of 0.50 to 0.72 Ϯ 0.42 in control subjects (P Ͻ 0.001), confirming that direct, donor-specific cellular immunity predominated in patients with CAN.

Therapeutic vaccinations can alter the strength of cellular and humoral alloimmunity in humans. The results suggest that serial immune monitoring of alloreactivity might be beneficial when immunizations are administered to potential transplant recipients.

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