Our previous work has shown that in mice polyomavirus-associated nephropathy (PVAN) requires both acute infection with mouse polyomavirus (MPyV) and an intact alloimmune response. The aim of this project was to determine the effect of MPyV infection on CD8 T cells specific for graft antigens.

Methods: Kidneys from B6 mice that express membrane-bound chicken ovalbumin (mOVA) were transplanted into nephrectomized, wildtype B6 mice in one of 3 groups: Group 1 – no treatment, Group 2 – transfer of 3-5 x 10^6 OT-I T cells (TCR transgenic CD8 T cells that recognize mOVA), and Group 3 – transfer of OT-I T cells and acute infection by MPyV. The number of CD8 and OT-I T cells in the transplanted kidneys were enumerated by flow cytometry. The function of graft-specific OT-I cells was assessed by ex vivo peptide stimulation and intracellular cytokine staining for IFN Γ.

Results: Consistent with previous findings untreated B6 recipients of mOVA kidneys (Group 1) or recipients that received OT-I T cells (Group 2) survived indefinely and had minimal evidence of renal injury. In contrast 9 of 10 recipients that received OT-I T cells and were acutely infected by MPyV (Group 3) developed severe PVAN and died. MPyV infection of recipients bearing mOVA kidneys without the transfer of OT-I T cells did not result in severe PVAN or recipient death.

MPyV infection increased the total number of CD8 T cells infiltrating transplanted kidneys (mean of 1.0×10^5 Group 2 vs. 3.1×10^5 Group 3) but had a lesser effect the number of graft-specific OT-I cells (mean of 1.8×10^4 Group 2 vs. 2.1 x10^4 Group 3). MPyV infection dramatically augmented the number of activated graft-specific OT-I cells within the kidney as assessed by IFN Γ production.

Conclusions: These findings demonstrate that MPyV infections have significant effects on the number and activation status of CD8 T cells capable of responding to antigens expressed by transplanted kidneys. They also suggest that PVAN may result at least in part from virally-induced augmentation of the alloimmune response.

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