Tu41 - KIR+CD8+ T Cells Target Pathogenic T Cells and are Active in Autoimmune Diseases and COVID-19

Tuesday, June 21, 2022

6:15 PM – 7:45 PM PT

Presenting Author(s)

JL

Jing Li, n/a

Postdoc
Stanford University
Palo Alto, California, United States

Co-Author(s)

MZ

Maxim Zaslavsky, n/a

Stanford University
Stanford, California, United States
YS

Yapeng Su, n/a

Institute for Systems Biology
Seattle, Washington, United States
JG

Jing Guo, n/a

Stanford University
Stanford, California, United States
Ms

Michael sikora, n/a

Stanford University
Stanford, California, United States
Vv

Vincent van Unen, n/a

postdoc
Stanford University
Stanford, California, United States
AC

Asbjørn Christophersen, n/a

University of Oslo
Oslo, Oslo, Norway
SC

Shin-Heng Chiou, n/a

Rutgers Cancer Institute of New Jersey
Rutgers, New Jersey, United States
LC

Liang Chen, n/a

Stanford University
Stanford, California, United States
JL

Jiefu Li, n/a

Stanford University
Stanford, California, United States
XJ

Xuhuai Ji, n/a

Stanford University
Stanford, California, United States
JW

Julie Wilhelmy, n/a

Stanford University
Stanford, California, United States
AM

Alana McSween, n/a

Stanford University
Stanford, California, United States
BP

Brad Palanski, n/a

Stanford University
Stanford, California, United States
VM

Vamsee Mallajosyula, n/a

Postdoctoral Scholar
Stanford University
Stanford, California, United States
NB

Nathan Bracey, n/a

Stanford University, Institute for Immunity, Transplantation and Infection
Stanford, California, United States
GD

Gopal Dhondalay, n/a

Stanford University
Stanford, California, United States
KB

Kartik Bhamidipati, n/a

Stanford University
Stanford, California, United States
JP

Joy Pai, n/a

Stanford University
Stanford, California, United States
LK

Lucas Kipp, n/a

Stanford University
Stanford, California, United States
JD

Jeffrey Dunn, n/a

Stanford University
Stanford, California, United States
SH

Stephen L. Hauser, n/a

University of California, San Francisco
San Francisco, California, United States
JO

Jorge Oksenberg, n/a

Professor
University of California, San Francisco
San Francisco, California, United States
Ansuman Satpathy, n/a

Assistant Professor
Stanford University
Stanford, California, United States
WR

William H. Robinson, n/a

Stanford University
Stanford, California, United States
LS

Lars Steinmetz, n/a

Stanford University
Stanford, California, United States
CK

Chaitan Khosla, n/a

Stanford University
Stanford, California, United States
Pu

Paul utz, n/a

Stanford University
Stanford, California, United States
LS

Ludvig Sollid, n/a

Professor, MD
Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway.
Stanford, California, United States
YC

Yueh-Hsiu Chien, n/a

Professor
Stanford University
Stanford, California, United States
James Heath, PhD

President and Professor
Institute for Systems Biology
Seattle, Washington, United States
NF

Nielsen Fernandez-Becker, n/a

Stanford University
Stanford, California, United States
KN

Kari C. Nadeau, n/a

Stanford University
Stanford, California, United States
NS

Naresha Saligrama, n/a

Washington University School of Medicine in St. Louis
St. Louis, Missouri, United States
Mark M. Davis, n/a

The Howard Hughes Medical Institute, Stanford University School of Medicine
Stanford, California, United States

Previous reports show a small subset of CD8⁺ T cells expressing Ly49 proteins in mice can suppress autoimmunity in a model of demyelinating disease. Here we find a markedly increased frequency of CD8⁺ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various human autoimmune diseases. Increased KIR⁺CD8⁺ T cells in the gut also correlate with disease activity in Celiac disease (CeD) patients. Moreover, KIR⁺CD8⁺ T cells can efficiently eliminate pathogenic gliadin-specific CD4⁺ T cells from CeD patients’ leukocytes in vitro. Together with gene expression data, this shows that these cells are the likely equivalent of the mouse Ly49⁺CD8⁺ T cells. Furthermore, we observe elevated levels of KIR⁺CD8⁺ T cells, but not CD4⁺ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Single-cell RNA and parallelized TCR sequencing reveals that expanded KIR⁺CD8⁺ T cells from these different diseases and healthy subjects display shared phenotypes and similar T cell receptor sequences. Selective ablation of the murine counterpart in virus-infected mice leads to exacerbated autoimmunity developed after infection. These results characterize a regulatory CD8⁺ T cell subset in humans which we hypothesize functions to control pathogenic cells in autoimmune and infectious diseases, with important implications for the cellular dynamics and possible therapeutic approaches to suppress unwanted autoimmunity.