¹Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig
²Klinik und Poliklinik für Kinder- und Jugendmedizin, pädiatrische Immunologie, Kinderrheumatologie und -infektiologie, Leipzig

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Introduction: Juvenile idiopathic arthritis (JIA) describes a heterogeneous group of several subtypes of chronic, autoimmune diseases characterized by an ongoing inflammation of the joints under the age of 16 [1]. While the subtypes differ in symptoms, therapy and pathogenesis, research has established a crucial role of CD4+ T cells in the pathogenesis of multiple subtypes [2]. SLAMF7 is a marker found on immune cells like NK cells and CD8+ T cells and is associated with cytotoxicity [3], [4]. Since cytotoxic CD4+ T cell populations (CD4 CTL) play an increasing role in inflammatory diseases, we were interested if CD4 CTLs are already detectable in JIA.

Methods: We isolated peripheral blood mononuclear cells (PBMCs) of children with JIA and a healthy age matched control group (HC) by using Ficoll density gradient. The PBMCs were stained for expression of surface markers (CD3, CD8, CD4, SLAMF7, CCR7, CD27, HLA-DR) and the intracellular marker Granzyme A. Cells were acquired on FACS LSR Fortessa (BD Biosciences) and analyzed using FlowJo V10 software.

Results: CD4+ T cells of children with JIA (n=27, p= 0.0202) showed a significantly higher expression of SLAMF7 on the surface compared to HC (n=3). Next, we analyzed SLAMF7+ on naïve, central memory and effector-memory CD4+ T cells, based on the expression of CCR7 and CD27. Especially naïve CD4+ T cells (CCR7+CD27+), showed a significantly higher expression of SLAMF7 in contrast to naïve CD4+ T cells of HC. Furthermore, SLAMF7+CD4+ T cells revealed a higher expression of Granzyme A and activation marker HLA-DR than their SLAMF7-CD4+ T cell counterparts and CD4+ T cells of HC.

Conclusion: In summary, we found an increased SLAMF7+CD4+ T cell population with potentially cytotoxic features. Since, SLAMF7 can act as an inhibitor or activator for immune cells, further investigations are necessary to examine the role of SLAMF7+CD4+ T cells in the pathogenesis of JIA.

The association between SLAMF7 expression and increased Granzyme A and HLA-DR levels implies that SLAMF7 may play a role in regulating T cell activation and effector functions in both health and disease states. To enhance our comprehension of this mechanism, an analysis of synovial fluid would be beneficial.

Disclosures: The authors and I declare that the research was conducted in the absence of financial or commercial relationships that could be construed as a potential conflict of interest.

References

[1] Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007 Mar 3;369(9563):767-78. DOI: 10.1016/S0140-6736(07)60363-8
[2] Zaripova LN, Midgley A, Christmas SE, Beresford MW, Baildam EM, Oldershaw RA. Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol Online J. 2021 Aug 23;19(1):135. DOI: 10.1186/s12969-021-00629-8
[3] Malaer JD, Marrufo AM, Mathew PA. 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) in systemic lupus erythematosus and cancer. Clin Immunol. 2019 Jul;204:50-6. DOI: 10.1016/j.clim.2018.10.009
[4] Gutierrez-Guerrero A, Mancilla-Herrera I, Maravillas-Montero JL, Martinez-Duncker I, Veillette A, Cruz-Munoz ME. SLAMF7 selectively favors degranulation to promote cytotoxicity in human NK cells. Eur J Immunol. 2022 Jan;52(1):62-74. DOI: 10.1002/eji.202149406