Role of Cytokines, Chemokines and IFN-γ+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis

Abstract

Multiple sclerosis is mediated by self-reactive myelin T and B cells that lead to axonal and myelin damage. The immune response in multiple sclerosis involves the participation of CD4+ T cells that produce cytokines and chemokines. This participation is important to find markers for the diagnosis and progression of the disease. In our work, we evaluated the profile of cytokines and chemokines, as well as the production of double positive CD4+ T cells for the production of IFNγ IL-17 in patients with multiple sclerosis, at different stages of the disease and undergoing different treatments. We found that relapsing–remitting patients had a significant increase in IL-12 production. About IL-5, its production showed significantly higher levels in secondarily progressive patients when compared to relapsing–remitting patients. IFN-γ production by PBMCs from secondarily progressive patients showed significantly higher levels. This group also had a higher percentage of CD4+ IFNγ+ IL-17+ T cells. The combination of changes in certain cytokines and chemokines together with the presence of IFNγ+ IL-17+ double positive lymphocytes can be used to better understand the clinical forms of the disease and its progression.

Distinct intrathecal inflammatory signatures following relapse and anti-COVID-19 mRNA vaccination in multiple sclerosis

“…These cytokines have also a relevant role in the pathophysiology of MS 1 and have also been associated with the peripheral response to vaccines. 9 RRMS patients showed increased basal levels of IL-12 when compared with healthy populations, 31,32 and higher IL-12 levels have been reported in the serum of RRMS patients during relapses. 31,32 IL-12 is also involved in immune responses induced by vaccines, regulating the differentiation of T cells, 33 and has been previously proposed as adjuvant of several vaccines in oncology, such as vaccine against melanoma, 34,35 and infectiology, such as toxoplasma gondii vaccine.…”

“…9 RRMS patients showed increased basal levels of IL-12 when compared with healthy populations, 31,32 and higher IL-12 levels have been reported in the serum of RRMS patients during relapses. 31,32 IL-12 is also involved in immune responses induced by vaccines, regulating the differentiation of T cells, 33 and has been previously proposed as adjuvant of several vaccines in oncology, such as vaccine against melanoma, 34,35 and infectiology, such as toxoplasma gondii vaccine. 36 IL-13 is an anti-inflammatory cytokine involved into Th2 differentiation, and is specifically increased in RRMS phenotype of MS when compared with healthy subjects and progressive MS. 32 Notably, levels of IL-13 have been proposed as T-cellular marker for SARS-CoV-2-specific T-cellular immune responses after infection and vaccination.…”

“…31,32 IL-12 is also involved in immune responses induced by vaccines, regulating the differentiation of T cells, 33 and has been previously proposed as adjuvant of several vaccines in oncology, such as vaccine against melanoma, 34,35 and infectiology, such as toxoplasma gondii vaccine. 36 IL-13 is an anti-inflammatory cytokine involved into Th2 differentiation, and is specifically increased in RRMS phenotype of MS when compared with healthy subjects and progressive MS. 32 Notably, levels of IL-13 have been proposed as T-cellular marker for SARS-CoV-2-specific T-cellular immune responses after infection and vaccination. 37 Finally, IL-1ra is a soluble antagonist of the IL-1 receptor that blocks IL-1β mediated-pro-inflammatory signaling, 38 and acts as an endogenous anti-inflammatory molecule in MS. 38 Increased levels of IL-1ra have been reported in MS especially during relapses 38 and is associated with mRNA COVID-19 vaccine response in murine models.…”

Distinct intrathecal inflammatory signatures following relapse and anti- COVID-19 mRNA vaccination in Multiple Sclerosis. A cross-sectional study.

“…IL-12 is also involved in immune responses induced by vaccines, regulating the differentiation of T cells [33], and has been previously proposed as adjuvant of several vaccines in oncology, such as vaccine against melanoma, [34,35] and infectiology, such as toxoplasma gondii vaccine [36]. IL-13 is an anti-in ammatory cytokine involved into Th2 differentiation, and is speci cally increased in RRMS phenotype of MS when compared with healthy subjects and progressive MS [32]. Notably, levels of IL-13 have been proposed as T-cellular marker for SARS-CoV-2 speci c T-cellular immune responses after infection and vaccination [37].…”

“…These cytokines have also a relevant role in the pathophysiology of MS [1] and have also been associated with the peripheral response to vaccines [9]. RRMS patients showed increased basal levels of IL-12 when compared with healthy populations [31,32], and higher IL-12 levels have been reported in the serum of RRMS patients during relapses [31,32]. IL-12 is also involved in immune responses induced by vaccines, regulating the differentiation of T cells [33], and has been previously proposed as adjuvant of several vaccines in oncology, such as vaccine against melanoma, [34,35] and infectiology, such as toxoplasma gondii vaccine [36].…”