CD8 T cells

Flip Flop Flip Flop….No wonder you are confused. We can’t make our mind up what is important. One week its CD4 next week its CD8. So at some point we will have a trial that aims to deplete CD8 in a specific way….Will it be a good thing and it be the answer I guess I daont know for definate but plenty of agents have impact in MS without having a major impact on CD8. The fear is it could make MS worse. The time seens to be coming when someone will do this. However the flip flopping only slows progress.

Characterization of antigen-specific CD8+ memory T cell subsets in peripheral blood of patients with multiple sclerosis.

Liu PJ, Yang TT, Fan ZX, Yuan GB, Ma L, Wang ZY, Lu JF, Yuan BY, Zou WL, Zhang XH, Liu GZ.Front Immunol. 2023 ;14:1110672. doi: 10.3389/fimmu.2023.1110672. eCollection 2023.PMID: 37215118 Free PMC article.

Background: Increasing evidence indicates the importance of CD8⁺ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8⁺ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity.

Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8⁺ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS.

Results: We found that MS patients had elevated frequency of MOG-specific CD8⁺ T cells, MOG-specific central memory T cells (T_CM), MOG-specific CD8⁺ effector memory T cells (T_EM), and MOG-specific CD8⁺ terminally differentiated cells (T_EMRA); elevated granzyme B expression on MOG-specific CD8⁺ T_CM; and, on MOG-specific CD8⁺ T_EM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8⁺ T_CM, granzyme B expression in CD8⁺ T_CM, and granzyme B and perforin expression on CD8⁺ T_EM, but with reduced PD-1 expression on CD8⁺ T_EM.

Conclusion: The dysregulation of antigen-specific CD8⁺ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.