Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Murine CD8+CD25+ T cells share phenotypic and functional features with CD4+Cd25+ regulatory T cells but do not protect against toxin induced murine chronic kidney disease

  • Deepika Mahajan, The University of Sydney at Westmead Millenium Institute, Australia
  • Dr Yiping Wang, The University of Sydney at Westmead Millenium Institute, Australia
  • Dr Vincent Lee, The University of Sydney at Westmead Millenium Institute, Australia
  • Prof David Harris, The University of Sydney at Westmead Millenium Institute, Australia

    • We have shown previously that reconstitution of Foxp3 expressing CD4+CD25+ T cells (Tregs) in SCID mice with established adriamycin nephropathy (AN) protected against progression of disease. CD8+CD25+ T cells have also been reported to exhibit regulatory activity. Here we investigated if CD8+CD25+ T cells share phenotypic features with Tregs in vitro and subsequently protect against toxin-induced murine chronic kidney disease. CD8+CD25+, CD8+CD25-, CD4+CD25+ and CD4+CD25- T cells were isolated from blood, spleen and lymph nodes of BALB/c mice using MACS beads. The production of various cytokines was examined by RT-PCR, ELISA and ELISPOT. To test the in vivo significance of CD8+CD25+ T cells, renal injury was induced in BALB/c mice by tail vein injection of 9.8 mg/kg Adriamycin. Different cells were injected intravenously after one week. We found that CD8+CD25+ T cells expressed and secreted TGFβ and IL-10, expressed GITR but not CTLA-4. CD8+CD25+ T cells expressed significantly less Foxp3 than CD4+CD25+ Tregs. Both CD4+CD25+ and CD8+CD25+ T cells inhibited proliferation of freshly isolated CD4+CD25- cells. Unlike CD4+CD25+ Tregs, reconstitution of CD8+CD25+ T cells did not provide protection against progression of renal injury in BALB/c mice with AN. These results demonstrate the existence of a subset of murine CD8+CD25+ T cells which share phenotypic and functional features with CD4+CD25+ Tregs, but are unable to protect against renal injury in vivo. The failure of CD8+CD25+ T cells to protect against renal injury is probably due to their low expression of FoxP3.

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