Life sustaining, full MHC-mismatched mouse kidney transplants are spontaneously accepted in certain strain combinations (e.g., DBA/2 to B6), while some full MHC-mismatched mouse kidneys are promptly rejected (e.g., C3H to B6). Heart allografts from either DBA/2 or C3H are promptly rejected by B6. Recent studies in our laboratory using the B6.Foxp3DTR system in mice showed that Foxp3+ cells (Tregs) are necessary to maintain tolerance of kidney allografts. Accepted kidneys contain distinctive Treg-rich organized lymphoid structures (TOLS).

Abundant CD11c+ dendritic cells (DCs) are evident in normal kidneys. In accepted kidney allografts, CD11c+ DCs are found in TOLS. These CD11c+ DCs are CD86low and may represent immature DCs and plasmacytoid DCs (pDCs). Flow cytometric analysis of DCs isolated from a DBA/2 kidney accepted by a B6 WT recipient confirmed the presence of CD11c+B220+ cells that co-stain with PDCA-1 (a pDC marker).

CD11c+ DCs isolated from native kidney and hearts from DBA/2 mice show the presence of PDCA-1+B220+ cells in kidneys but not in hearts, a potential basis for different tolerogenicity of these organs. Native kidneys from C3H also show the presence of pDCs. We assessed the ability of pDCs from DBA/2 and C3H to convert Teff to Treg, using B6.Foxp3GFP cells as responders. pDCs were isolated by negative selection from bone marrow (BM) to greater than 95% purity. Splenic CD4+CD25- cells from B6.Foxp3GFP mice were converted to GFP+Foxp3+ cells after 4 days of culture with allogeneic DBA/2 pDCs in the presence of IL2 and TGFΒ as determined by flow cytometry. pDCs isolated from C3H bone marrow were not as efficient in converting Teff to Tregs (Figure 1). Data are represented as means ± S.E. of triplicate samples. All data are representative of two independently performed experiments.

We conclude that the content of pDCs in the kidney vs. the heart as well as the strain potency of pDCs to convert Teff to Tregs contribute to kidney allograft acceptance.

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