tetano
Editor, Senior Moderator
Front Immunol
. 2024 May 30:15:1306490.
doi: 10.3389/fimmu.2024.1306490. eCollection 2024. Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8[SUP]+[/SUP] T cell repertoire response to influenza vaccination
Sara E Sabbagh[SUP] #[/SUP][SUP] 1 [/SUP], Dipica Haribhai[SUP] #[/SUP][SUP] 1 [/SUP], Jill A Gershan[SUP] 2 [/SUP], James Verbsky[SUP] 1 [/SUP], James Nocton[SUP] 1 [/SUP], Maryam Yassai[SUP] 3 [/SUP], Elena N Naumova[SUP] 4 [/SUP], Erin Hammelev[SUP] 1 [/SUP], Mahua Dasgupta[SUP] 5 [/SUP], Ke Yan[SUP] 5 [/SUP], Jack Gorski[SUP] 3 [/SUP], Calvin B Williams[SUP] 1 [/SUP]
Affiliations
Recurrent exposures to a pathogenic antigen remodel the CD8[SUP]+[/SUP] 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, M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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.
Keywords: CD8 + T cells; T cell repertoire; clonotype diversity; clonotypes; influenza vaccination; juvenile idiopathic arthritis.
. 2024 May 30:15:1306490.
doi: 10.3389/fimmu.2024.1306490. eCollection 2024. Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8[SUP]+[/SUP] T cell repertoire response to influenza vaccination
Sara E Sabbagh[SUP] #[/SUP][SUP] 1 [/SUP], Dipica Haribhai[SUP] #[/SUP][SUP] 1 [/SUP], Jill A Gershan[SUP] 2 [/SUP], James Verbsky[SUP] 1 [/SUP], James Nocton[SUP] 1 [/SUP], Maryam Yassai[SUP] 3 [/SUP], Elena N Naumova[SUP] 4 [/SUP], Erin Hammelev[SUP] 1 [/SUP], Mahua Dasgupta[SUP] 5 [/SUP], Ke Yan[SUP] 5 [/SUP], Jack Gorski[SUP] 3 [/SUP], Calvin B Williams[SUP] 1 [/SUP]
Affiliations
- PMID: 38873594
- PMCID: PMC11169902
- DOI: 10.3389/fimmu.2024.1306490
Recurrent exposures to a pathogenic antigen remodel the CD8[SUP]+[/SUP] 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, M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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 M1[SUB]58-66[/SUB] 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.
Keywords: CD8 + T cells; T cell repertoire; clonotype diversity; clonotypes; influenza vaccination; juvenile idiopathic arthritis.