TY - JOUR
T1 - Evolution of cytomegalovirus-responsive T cell clonality following solid organ transplantation
AU - Higdon, Lauren E.
AU - Schaffert, Steven
AU - Huang, Huang
AU - Montez-Rath, Maria E.
AU - Lucia, Marc
AU - Jha, Alokkumar
AU - Saligrama, Naresha
AU - Margulies, Kenneth B.
AU - Martinez, Olivia M.
AU - Davis, Mark M.
AU - Khatri, Purvesh
AU - Maltzman, Jonathan S.
N1 - Funding Information:
Research of the National Institute of Allergy and Infectious Diseases (T32 AI07290 to L.E.H.) and National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007357-31 to L.E.H.), and National Institute of Allergy and Infectious Diseases Grants 1U19AI109662, U19AI057229, and 5R01AI125197 (to P.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. P.K. is funded by the Bill and Melinda Gates Foundation (OPP1113682), Department of Defense contracts W81XWH-18-1-0253 and W81XWH1910235, and the Ralph & Marian Falk Medical Research Trust outside of the work presented in this study.
Funding Information:
This work was supported by the American Heart Association (Award 13IRG13640042 to J.S.M.), the American Heart Association/Enduring Hearts (Grant 17POST33660597 to L.E.H.), Veterans Affairs Clinical Science Research and Development (Award 1I01CX001971 to J.S.M.), the National Institute of Diabetes and Digestive and Kidney Diseases (K01 1K01DK123196 to L.E.H.), the Stanford Translational Research and Applied Medicine Program (to L.E.H.), support from the Division of Intramural
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
PY - 2021/10/15
Y1 - 2021/10/15
N2 - CMV infection is a significant complication after solid organ transplantation. We used single cell TCR ab sequencing to determine how memory inflation impacts clonality and diversity of the CMV-responsive CD8 and CD4 T cell repertoire in the first year after transplantation in human subjects. We observed CD8 T cell inflation but no changes in clonal diversity, indicating homeostatic stability in clones. In contrast, the CD4 repertoire was diverse and stable over time, with no evidence of CMV-responsive CD4 T cell expansion. We identified shared CDR3 TCR motifs among patients but no public CMV-specific TCRs. Temporal changes in clonality in response to transplantation and in the absence of detectable viral reactivation suggest changes in the repertoire immediately after transplantation followed by an expansion with stable clonal competition that may mediate protection.
AB - CMV infection is a significant complication after solid organ transplantation. We used single cell TCR ab sequencing to determine how memory inflation impacts clonality and diversity of the CMV-responsive CD8 and CD4 T cell repertoire in the first year after transplantation in human subjects. We observed CD8 T cell inflation but no changes in clonal diversity, indicating homeostatic stability in clones. In contrast, the CD4 repertoire was diverse and stable over time, with no evidence of CMV-responsive CD4 T cell expansion. We identified shared CDR3 TCR motifs among patients but no public CMV-specific TCRs. Temporal changes in clonality in response to transplantation and in the absence of detectable viral reactivation suggest changes in the repertoire immediately after transplantation followed by an expansion with stable clonal competition that may mediate protection.
UR - http://www.scopus.com/inward/record.url?scp=85116577749&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2100404
DO - 10.4049/jimmunol.2100404
M3 - Article
C2 - 34551964
AN - SCOPUS:85116577749
SN - 0022-1767
VL - 207
SP - 2077
EP - 2085
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -