Quantity and Functions of CD4–CD8– Double Negative (DN) αβ T Cells in Kidney Is MHC Dependent.
Johns Hopkins University, Baltimore, MD
Meeting: 2017 American Transplant Congress
Abstract number: B48
Keywords: Inflammation, Kidney transplantation, Major histocompatibility complex (MHC)
Session Name: Poster Session B: Allorecognition and T Cell Biology
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
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.
|Percentage of T cells|
|Mouse groups||DN T cells||CD4+T cells||CD8+T cells|
|WT||18.6 ± 3||54 ± 4||26± 4|
|MHC class-I KO||13 ± 3*||83 ± 4||2 ± 1*|
|MHC class-II KO||31 ± 1||14 ± 4*||50 ± 4|
|WT||4 ± 2||63 ± 6||33 ±3|
|MHC class-I KO||2 ± 1*||98 ± 1||1± 0.1*|
|MHC class-II KO||7 ± 2||4 ± 1*||85 ± 4|
|WT||2± 1||75 ± 2||15 ± 1|
|MHC class-I KO||1 ± 1*||90 ± 2||1 ± 1*|
|MHC class-II KO||5 ± 1||17 ± 2*||43 ± 1|
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).
To cite this abstract in AMA style: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. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/quantity-and-functions-of-cd4-cd8-double-negative-dn-t-cells-in-kidney-is-mhc-dependent/. Accessed March 26, 2023.
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