Abstract

Disruption of the non-classical Major Histocompatibility Complex (MHC) Ib molecule Qa-1 impairs CD8 Treg and natural killer (NK) cell function and promotes a lupus-like autoimmune disease. This immune perturbation would be expected to enhance anti-transplant responses and impair tolerance induction, but the effect of Qa-1 deficiency on the transplant response has not been previously reported. Qa-1 deficiency enhanced CD4 TFH and germinal center (GC) B cell numbers in naïve mice and hastened islet allograft rejection. Despite enhanced immunity in B6.Qa-1−/− mice, these mice did not generate an excessive primary CD4 TFH cell response nor an enhanced alloantibody reaction. Both CD8 Tregs and NK cells, which often regulate other cells through host Qa-1 expression, were targets of anti-CD45RB therapy that had not been previously recognized. However, B6.Qa-1−/− mice remained susceptible to anti-CD45RB mediated suppression of the alloantibody response and transplant tolerance induction to mismatched islet allografts. Overall, despite enhanced immunity as demonstrated by augmented CD4 TFH/GC B cell numbers and hastened islet allograft rejection in naïve 12-week old Qa-1 deficient mice, the CD8 Treg/NK cell restriction element Qa-1 does not regulate the primary cellular or humoral alloresponse and is not required for long-term transplant tolerance.

Details

Title
Host Expression of the CD8 Treg/NK Cell Restriction Element Qa-1 is Dispensable for Transplant Tolerance
Author
Stocks, Blair T 1 ; Wilson, Christopher S 1 ; Marshall, Andrew F 2 ; Brewer, Lauren A 2 ; Moore, Daniel J 3   VIAFID ORCID Logo 

 Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA 
 Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, TN, USA 
 Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA; Department of Pediatrics, Ian Burr Division of Endocrinology and Diabetes, Vanderbilt University Medical Center, Nashville, TN, USA 
Pages
1-8
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1953983599
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.