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Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8+ T cell repertoire response to influenza vaccination. Front Immunol 2024;15:1306490

Date

06/14/2024

Pubmed ID

38873594

Pubmed Central ID

PMC11169902

DOI

10.3389/fimmu.2024.1306490

Scopus ID

2-s2.0-85195642328 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Recurrent exposures to a pathogenic antigen remodel the CD8+ T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M158-66 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M158-66 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M158-66 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M158-66 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.

Author List

Sabbagh SE, Haribhai D, Gershan JA, Verbsky J, Nocton J, Yassai M, Naumova EN, Hammelev E, Dasgupta M, Yan K, Gorski J, Williams CB

Authors

James J. Nocton MD Professor in the Pediatrics department at Medical College of Wisconsin
Sara Sabbagh DO Assistant Professor in the Pediatrics department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Arthritis, Juvenile
CD8-Positive T-Lymphocytes
Child
Child, Preschool
Clone Cells
Female
Humans
Immunologic Memory
Influenza Vaccines
Influenza, Human
Male
Vaccination
Young Adult