Author Of 1 Presentation
P0952 - Characterization of age-related changes in circulating T cells in multiple sclerosis and normal controls: a pilot study (ID 975)
Abstract
Background
Immunosenescence (ISC) is characterized by age-associated changes in immune system composition and function. Multiple sclerosis (MS) is a lifelong illness, hence the disease process is superimposed on, and may interact bi-directionally with, ISC such that ISC may alter disease activity, while cumulative inflammatory events in MS may influence ISC. Since the T cell compartment is markedly affected by ISC, we hypothesized that T-cell aging may differ between MS patients and normal controls (NCs).
Objectives
To characterize age-related changes in circulating T cells in treatment-naïve multiple sclerosis patients compared to NCs.
Methods
Frequencies of circulating T-cell subsets were determined using multiparametric flow cytometry of peripheral blood mononuclear cells from 50 NC (Mean Age 48.6, Range 20 – 84) and 40 treatment-naïve MS (Mean Age 43.3, Range 18 – 72). Age-related changes in T cell subsets, and differences in T cell ISC between NC and MS, were determined using linear mixed effects models.
Results
Age-related changes in circulating T-cell subsets in the NCs recapitulated known features of ISC, including reductions in recent thymic emigrants and reciprocal changes in CD4 and CD8 T cells as well as in naïve and memory T cells. While most aspects of T cell ISC in MS patients were similar to those observed in NC, MS patients experienced early and persistent redistribution of the naïve and memory CD4 T cell compartment, such that at any given age, frequencies of circulating naïve (CCR7+CD45RA+) CD4 T cells were 16.7% lower and frequencies of effector memory (CCR7-CD45RA-) CD4 T cells were 14.5% greater on average than NC. Further, aged MS patients exhibited a relative increase in activated (HLA-DR+CD38+) and cytotoxic (CCL5+EOMES+) CD4 T cells compared to NC, while they did not exhibit increased CLA+ CD4 T cells. Lastly, aged MS patients exhibited altered immune checkpoint-molecule expression, wherein frequencies of CTLA-4+ CD8 T cells did not increase with age as was seen in NC.
Conclusions
Most T-cell subsets followed similar aging trajectories in MS patients and NCs, indicating normal ISC is largely conserved in MS. Nonetheless, key differences suggest that aged MS patient T cells exhibit increased propensity for immune activation and effector function compared to NC, which may reflect ongoing inflammation and injury throughout the lifespan. Further elucidation of ISC in MS may inform management of immune therapies in aging MS patients.
Presenter Of 1 Presentation
P0952 - Characterization of age-related changes in circulating T cells in multiple sclerosis and normal controls: a pilot study (ID 975)
Abstract
Background
Immunosenescence (ISC) is characterized by age-associated changes in immune system composition and function. Multiple sclerosis (MS) is a lifelong illness, hence the disease process is superimposed on, and may interact bi-directionally with, ISC such that ISC may alter disease activity, while cumulative inflammatory events in MS may influence ISC. Since the T cell compartment is markedly affected by ISC, we hypothesized that T-cell aging may differ between MS patients and normal controls (NCs).
Objectives
To characterize age-related changes in circulating T cells in treatment-naïve multiple sclerosis patients compared to NCs.
Methods
Frequencies of circulating T-cell subsets were determined using multiparametric flow cytometry of peripheral blood mononuclear cells from 50 NC (Mean Age 48.6, Range 20 – 84) and 40 treatment-naïve MS (Mean Age 43.3, Range 18 – 72). Age-related changes in T cell subsets, and differences in T cell ISC between NC and MS, were determined using linear mixed effects models.
Results
Age-related changes in circulating T-cell subsets in the NCs recapitulated known features of ISC, including reductions in recent thymic emigrants and reciprocal changes in CD4 and CD8 T cells as well as in naïve and memory T cells. While most aspects of T cell ISC in MS patients were similar to those observed in NC, MS patients experienced early and persistent redistribution of the naïve and memory CD4 T cell compartment, such that at any given age, frequencies of circulating naïve (CCR7+CD45RA+) CD4 T cells were 16.7% lower and frequencies of effector memory (CCR7-CD45RA-) CD4 T cells were 14.5% greater on average than NC. Further, aged MS patients exhibited a relative increase in activated (HLA-DR+CD38+) and cytotoxic (CCL5+EOMES+) CD4 T cells compared to NC, while they did not exhibit increased CLA+ CD4 T cells. Lastly, aged MS patients exhibited altered immune checkpoint-molecule expression, wherein frequencies of CTLA-4+ CD8 T cells did not increase with age as was seen in NC.
Conclusions
Most T-cell subsets followed similar aging trajectories in MS patients and NCs, indicating normal ISC is largely conserved in MS. Nonetheless, key differences suggest that aged MS patient T cells exhibit increased propensity for immune activation and effector function compared to NC, which may reflect ongoing inflammation and injury throughout the lifespan. Further elucidation of ISC in MS may inform management of immune therapies in aging MS patients.