People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs

Abstract

The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4+ and CD8+ T cells and activated HLA-DR+ Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56dimCD57+ NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity.

Repeated iv anti‐CD20 treatment in multiple sclerosis: Long‐term effects on peripheral immune cell subsets

“…While the neuropathological features in the brain of patients with relapsing or progressive MS are essentially similar, the relative incidence of different lesion characteristics change with time of disease evolution. 33 OCR is an effective treatment for both RR-and PP-MS, and CD20 + B cells are thought to act as cytokine and antibody producers or as antigen-presenting cells essential for T-cell activation in both relapsing and progressive MS. 33 As for progressive disease, longer disease duration and a higher degree of disability were shown to correlate only with NK cell subsets alterations in patients with PP-MS. 33 Concerning T cells, results were inconsistent, as patients with progressive disease might have lower numbers of effector memory CD4 + T cells or a lower percentage of both naive and effector memory CD8 + T cells compared to healthy controls. 33 However, it was suggested that memory T-cell subsets might differ among relapsing and progressive MS. 33 Furthermore, TH17 subsets were shown to be increased in both PP-and SP-MS patients.…”

“…33 OCR is an effective treatment for both RR-and PP-MS, and CD20 + B cells are thought to act as cytokine and antibody producers or as antigen-presenting cells essential for T-cell activation in both relapsing and progressive MS. 33 As for progressive disease, longer disease duration and a higher degree of disability were shown to correlate only with NK cell subsets alterations in patients with PP-MS. 33 Concerning T cells, results were inconsistent, as patients with progressive disease might have lower numbers of effector memory CD4 + T cells or a lower percentage of both naive and effector memory CD8 + T cells compared to healthy controls. 33 However, it was suggested that memory T-cell subsets might differ among relapsing and progressive MS. 33 Furthermore, TH17 subsets were shown to be increased in both PP-and SP-MS patients. 34 Another important factor that needs to be considered is age, even more so as the number of elderly MS patients will continue to grow due to an increased life expectancy among the general population as well as the availability of disease-modifying therapies.…”

“…While the neuropathological features in the brain of patients with relapsing or progressive MS are essentially similar, the relative incidence of different lesion characteristics change with time of disease evolution 33 . OCR is an effective treatment for both RR‐ and PP‐MS, and CD20 + B cells are thought to act as cytokine and antibody producers or as antigen‐presenting cells essential for T‐cell activation in both relapsing and progressive MS 33 . As for progressive disease, longer disease duration and a higher degree of disability were shown to correlate only with NK cell subsets alterations in patients with PP‐MS 33 .…”

“…OCR is an effective treatment for both RR‐ and PP‐MS, and CD20 + B cells are thought to act as cytokine and antibody producers or as antigen‐presenting cells essential for T‐cell activation in both relapsing and progressive MS 33 . As for progressive disease, longer disease duration and a higher degree of disability were shown to correlate only with NK cell subsets alterations in patients with PP‐MS 33 . Concerning T cells, results were inconsistent, as patients with progressive disease might have lower numbers of effector memory CD4 + T cells or a lower percentage of both naive and effector memory CD8 + T cells compared to healthy controls 33 .…”

Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques

“…It appears in the late-stage activation of T cells and can serve as a marker of activated T cells ( 53 ). HLA-DR + T cells are thought of highly proliferative and short-lived ( 54 ) and HLA-DR + Tregs subset is described to be more cytotoxic ( 55 ). Report revealed that HLA-DR + T cells are elevated in SFTSV-infected patients ( 53 ).…”