Session Information
Date: Sunday, November 12, 2023
Title: (0066–0095) T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster
Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Background: GMCSF producing T-cells may be implicated in the pathogenesis of autoimmune diseases like rheumatoid arthritis (RA), multiple sclerosis (MS) and psoriatic arthritis. Few studies reported higher frequencies of CD4+GMCSF+ T-cells in the MS lesions and RA synovial fluid; however, there is no data on CD8+GMCSF+ T-cells. Thus, we planned to assess their frequencies in blood and synovial fluid, and characterize based on polyfunctionality, phenotype, cytotoxic ability and the effect of methotrexate on them.
Methods: The frequency of GMCSF producing CD8 and CD4 T-cells was assessed by stimulation with PMA/Ionomycin, followed by immunostaining and flowcytometry. Subsequently, polyfunctionality for other cytokines (TNFα, IFNγ and IL-17), memory/naïve phenotype and perforin/granzyme expression was also assessed by flowcytometry
Results: Enrichment of GMCSF producing T-cells was found in the synovial fluid, with elevated frequencies of both CD8+GMCSF+ T-cells (5.8, 3.9%, p= 0.0045) and CD4+GMCSF+ T-cells (8.5, 4.5%, p=0.0008) compared to peripheral blood. These cells were characterised as extremely polyfunctional, with higher frequencies of triple cytokine positive GMCSF+TNFα+IFNγ positive CD8 T-cells (81, 36%, p=0.049) and CD4+GMCSF+TNFα+IFNγ+ (48, 32%, p=0.01)) in synovial fluid compared to blood. Majority of GMCSF producing T-cells had an effector memory (EM) phenotype, besides CD8+GMCSF+ T-cells also having increased expression of granzyme B. After MTX treatment, there was a significant reduction in circulating CD4+ T-cells producing GMCSF (4.6% to 2.9%, p= 0.0014) and a similar trend was seen in the CD8 T (3.7% to 2.9% p= 0.068) cells.
Conclusion: Synovial fluid enrichment with GMCSF producing CD8 T-cells (and CD4 T-cells) was observed, demonstrating elevated polyfunctionality and granzyme B expression with majority belonging to EM phenotype. Upon treatment with methotrexate a reduction in the frequencies of these cells was found.
To cite this abstract in AMA style:
KHULLAR A, Dhir V, Bidyalaxmi L, Prasad C, Jayaprakash S, Jain S, Saikia B, Sharma A, Sharma S, Yadav A, Naidu S, Jain S. Characterizing GMCSF Producing T-cells in Rheumatoid Arthritis and Effect of Methotrexate on Them [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/characterizing-gmcsf-producing-t-cells-in-rheumatoid-arthritis-and-effect-of-methotrexate-on-them/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterizing-gmcsf-producing-t-cells-in-rheumatoid-arthritis-and-effect-of-methotrexate-on-them/