Background: Prior studies have established important roles of CD4⁺ T cells, natural killer T cells, and CD4⁺CD25⁺FoxP3⁺ Tregs in kidney ischemia reperfusion injury (IRI) pathogenesis. Recently, CD4⁻CD8⁻ (double-negative; DN) T cells have been found in mouse and human kidney, and directly improve outcomes in experimental IRI (J Am Soc Neph 2015). The role of MHC in T cell selection and maturation in thymus is well characterized (Trends Immunol, 2012). However, little is known about the immuno-biology and the MHC restriction of DN cells in kidney. We hypothesized that MHC restricts the quantity and function of kidney DN T cells.

Methods: C57BL6-β2m MHC class-I, MHC class-II knockout (KO) and WT control mice were used to determine the MHC restriction kidney DN T cells (n=3-4). The lymphocytes from the kidneys, lymph node (LN) and thymus were analyzed by flow cytometry.

Results: Kidneys from both class I and class II MHC KO mice have reduced total numbers of DN T cells compared to WT controls (WT, 3,355±1,077 vs. MHC I KO, 1,016±471 vs. MHC II KO, 1,538±639; P<0.01). DN T cell numbers in LN were (WT, 16,546± 1,740 vs MHC I KO, 9,383± 372 vs MHC II KO, 21,988±7,157) and in thymus were 19,735±7,681 in WT, 7,610±3,215 in MHC I KO and 26,390±6150 in MHC II KO (P<0.05). We also evaluated the frequency of DN T cells in comparison to CD4⁺ & CD8⁺ cells in kidney, LN and thymus.

Conclusion: These data demonstrate that DN T cells in the kidney have similarities but also unique MHC restriction compared to other lymphoid organs. Further dissection of kidney DN T cell biology will help us understand the pathogenesis of IRI as well as other T cell rejection.

CITATION INFORMATION: Sadasivam M, Noel S, Lee S, Hamad A, Rabb H. Quantity and Functions of CD4^–CD8^– Double Negative (DN) αβ T Cells in Kidney Is MHC Dependent. Am J Transplant. 2017;17 (suppl 3).

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