Multiple sclerosis therapies differentially impact SARS-CoV-2 vaccine-induced antibody and T cell immunity and function

Abstract Polycythaemia vera (PV) is a clonal disorder arising from a pluripotent hematopoietic progenitor cell. The etiology of PV remains unknown and there is no consensus as to the optimal therapy for this disorder. T regulatory (Treg) cells play a vital role in the maintenance of self-tolerance, control of auto-immunity and regulation of T-cell homeostasis, and they modulate overall immune responses against a variety of pathogens. Recent studies revealed that Treg cells play a crucial role in the process of hematopoietic activity. However, the effect of Treg cells in PV has not been reported. The Treg cells might participate in the dysfunction of T-cell immunity in PV. The profile and function of Treg cells in PV patients were explored in this study. Peripheral blood was withdrawn from 21 PV patients (Female 8 ; Male 13), as well as 25 age-matched healthy donors (F 9 ; M 16) as controls. All samples were taken after informed consent and collected from PV patients prior to treatment. Diagnoses of PV were made according to clinical and laboratory criteria. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analyses after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Real-time PCR and Western blotting were also performed to identify quantitative FOXP3 mRNA expression and protein level in the PBMCs from PV in comparison to controls. The relationships between the percentage of Treg cells, the expressions for quantitative mRNA and protein, with the clinical data were assessed. The percentage of CD4+ T-cells was significant decreased in the group of PV than in normal control (28.7±7.07% vs 38.6±8.38%, p<0.05). But the percentage of CD4+CD25+FOXP3+ T-cells (Treg cells) in PV patients was significantly increased when compared to the control (10.93±4.02% vs 5.86±1.99%, p<0.05). Moreover, the quantitative mRNA expression of FOXP3 (64.23±18.52 vs 16.06±4.78, p<0.05) and protein expression of FOXP3 (0.74±0.16 vs 0.62±0.10, p<0.05)) were significantly enhanced in PV patients (shown in Figure 1). In conclusion, we showed that patients with PV have enhanced percentage of Treg cells in their peripheral blood. This was substantiated further with the finding that overexpressions of FOXP3 in PV both in mRNA and protein level. These results highlight important Treg-cell abnormalities in patients with PV because natural Treg cells are significantly increased in number and function. The underlying mechanism is still undefined, but the increased frequency and function of Treg cells might account for the abnormal T cell immunity in PV patients. It was suggested that there may be differently suppressive machanisms for Treg in these patients. The elevated Treg cells in PV might be activated and then affect the hematopoietic activity. We believe that Treg cells might involved in the dysfunction of T/NK cells in their disability to downregulate the hematopoietic proliferation in PV. And the expansion of Treg cells may be a feature of PV and associated with the pathogenesis of PV. Further investigation in this abnormality might provide novel therapy clue for this disease. Figure Figure

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Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection

Journal of Experimental Medicine ◽

10.1084/jem.20160758 ◽

2017 ◽

Vol 214 (3) ◽

pp. 651-667 ◽

Cited By ~ 66

Author(s):

Claire L. Gordon ◽

Michelle Miron ◽

Joseph J.C. Thome ◽

Nobuhide Matsuoka ◽

Joshua Weiner ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Virus Detection ◽

Distribution Patterns ◽

T Cell Immunity ◽

T Cell Homeostasis ◽

Intrinsic Factors ◽

Cell Immunity ◽

Human Cmv ◽

And Function

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan.

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DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis

Frontiers in Bioscience ◽

10.2741/2849 ◽

2008 ◽

Vol 13 (13) ◽

pp. 2356 ◽

Cited By ~ 37

Author(s):

Dirk Reinhold

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

T Cell Immunity ◽

Cell Immunity

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STAT5 and CD4+ T Cell Immunity

F1000Research ◽

10.12688/f1000research.9838.1 ◽

2017 ◽

Vol 6 ◽

pp. 32 ◽

Cited By ~ 18

Author(s):

David L. Owen ◽

Michael A. Farrar

Keyword(s):

T Cell ◽

Regulatory T Cell ◽

Critical Role ◽

Cell Types ◽

T Cell Immunity ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Cell Immunity ◽

And Function

STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4+ helper and regulatory T-cell subsets.

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