Background/Purpose: A variety of T cells such as Th1, Th2, Th9, Th17, NKT, MAIT, etc have been attributed to multiple autoimmune diseases.  In psoriatic arthritis (PsA) contributing role of the Th17 cells have been observed and lately success of IL17/IL-23 targeted therapies has further substantiated this. Here we will share our cumulative data on Th17 cells in PsA collected over last 2 decades. 

Methods: PBMCs and synovial fluid mononuclear cells (SFMCs) were collected from age/sex matched with active untreated PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA, n=50, each). Patients were recruited after proper IRB approval. Magnetically sorted CD3⁺ T cells were isolated from PBMCs and SFMCs; were activated (10⁶ cells/ml) with anti-human CD3/CD28 antibody cocktail and cultured in RPMI medium for 5 days.  Hi-D FACS studies were performed; lymphocytes were gated first based on FSC and SSC, then CD3⁺CD11a⁺CD45RO⁺17A⁺ cells were gated. In these gated population MAIT cells were identified as CD3⁺CD161⁺Vα7.2TCR⁺ cells, γδ-T cells as CD3⁺ γδTCR⁺, NKT cells as CD3⁺CD161⁺ and αβ-T cells as αβTCR⁺. NKT cells (CD3⁺CD161⁺) were further gated for TCR Vα24-Jα18 (iNKT cell) ab positivity.

Results: In OA activated Effector Memory T Cells (TEM cells) were < 1%. We noticed a marked polyfunctionality in PBMC/SFMC T cells both in PsA and RA. In PsA SFMC, memory T cells (CD3+CD4+CD45RO+) had IL-17A+ (18+0.5%), IL-22+(7+0.3%) and IL-23R+ (8.5+0.5%) T cells compared to SFMC memory T cells of RA (6.8+0.3%, 2.5+0.5%, 2.1+0.7%, respectively; p< 0.001). TEM cells in PsA and RA at single cell level also produced IL-9 and TNF-α.

IL-17A⁺ TEM phenotypes in SFMC of PsA demonstrated both invariant and conventional αβT cell Immune response (Fig 1): αβTCR⁺ (79.8+0.9%), γδ TCR⁺ (1.5+0.2%), iNKT (15.5+1.1%) and MAIT (4.5+0.8%) cells. Majority of the αβTCR⁺ T cells were CD4+ ( >85%) whereas MAIT were predominantly CD8⁺ (~ 90%).

Conclusion: In PsA TEM cells were polyfunctional in respect to their cytokines (IL-9, IL-17A,IL-22, TNF-α)  however more skewed towards conventional activated memory αβTh17 cells. Our finding clearly suggests that TEM cells of adaptive as well as innate immune response produce IL-17A in PsA, but the major amount of IL-17A comes from the conventional CD4⁺ (αβTCR⁺) cells (~80%). The fact that synovial T cells of innate immune response also express IL-17A (~20%), suggest a bridge between adaptive and innate immune response.

Figure 1: IL-17A+ cells in peripheral blood and synovial fluid of PsA patients. Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolated from PsA (n=15) and stimulated with with anti-human CD3/CD28 antibody cocktail. Lymphocytes were gated first based on FSC and SSC, then CD3+CD11a+CD45RO+17A+ T cells were gated. αβ TCR+, γδ TCR+ T cells, iNKT and MAIT cells were identified in these gated CD3+CD11a+CD45RO+17A+. (A) Representative FACS plots showing the frequencies of different IL-17A+ immune cells in PsA. (B) Bar diagram (n=15) showing the frequencies of IL-17A producing αβ, NKT, γδ T cells and MAIT cells in PBMC and SFMC of PsA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/t-cells-with-il-17a-signature-in-psoriatic-arthritis-are-of-different-subpopulations-and-are-polyfuntional/