The CD4+ T-cell subset lacking expression of the CD28 costimulatory molecule is expanded and shows a higher activation state in multiple sclerosis

Pinto-Medel, María Jesús; García-León, Juan Antonio; Oliver-Martos, Begoña; Lopez‐Gómez, Carlos; Luque, Gloria M.; Arnáiz-Urrutia, Carlos; Órpez, Teresa; Marín-Bañasco, Carmen; Fernández, Óscar; Leyva, Laura

doi:10.1016/j.jneuroim.2011.11.008

Cited by 21 publications

(12 citation statements)

References 51 publications

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“…were observed in other chronic antigen stimulations, without complete characterization of their phenotype or effector functions (30)(31)(32)(33)(34)(35). The chCD4s present in patients with cancer are probably related to these previously described subsets.…”

Section: Discussionmentioning

confidence: 91%

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High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

et al. 2014

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CD4þ T cells influence tumor immunity in complex ways that are not fully understood. In this study, we characterized a population of human differentiated effector CD4 þ T cells that is defined by low levels of the interleukin (IL)-2 and IL-7 receptors (CD25 À CD127 À ). We found that this cell population expands in patients with various types of cancer, including breast cancer, to represent 2% to 20% of total CD4 þ blood T lymphocytes as compared with only 0.2% to 2% in healthy individuals. Notably, these CD25 À

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Section: Discussionmentioning

confidence: 91%

“…Indeed, these features have been observed in diseases in which chronic antigen stimulation is obvious, such as HIV infection (27,29,30), or hypothesized, such as rheumatoid arthritis and multiple sclerosis (31)(32)(33)(34)(35). In mUMs, CD28 expression was low on effector chCD4s (Fig.…”

Section: Chcd4 T Cells Are Highly Differentiated Effector Cells In Pamentioning

confidence: 89%

High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

et al. 2014

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“…It has been suggested that autoantigens can lead to clonal expansion of these cells. Thus, there are reports [45, 46] indicating how they can, for instance, show reactivity to myelin basic protein (MBP). The presence of CD4 + CD28 − T cells in both elderly individuals and patients with autoimmune diseases (ADs) has supported the concept that ADs are closely related to the cell aging process.…”

Section: Immunosenescencementioning

confidence: 99%

Immunosenescence, Aging, and Systemic Lupus Erythematous

Montoya-Ortiz

2013

Autoimmune Diseases

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Senescence is a normal biological process that occurs in all organisms and involves a decline in cell functions. This process is caused by molecular regulatory machinery alterations, and it is closely related to telomere erosion in chromosomes. In the context of the immune system, this phenomenon is known as immunosenescence and refers to the immune function deregulation. Therefore, functions of several cells involved in the innate and adaptive immune responses are severely compromised with age progression (e.g., changes in lymphocyte subsets, decreased proliferative responses, chronic inflammatory states, etc.). These alterations make elderly individuals prone to not only infectious diseases but also to malignancy and autoimmunity. This review will explore the molecular aspects of processes related to cell aging, their importance in the context of the immune system, and their participation in elderly SLE patients.

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“…During the development of MS, autoreactive T cells and macrophages which are stimulated in peripheral lymphoid tissues, infiltrate into the CNS and produce inflammatory molecules, leading to oligodendrocyte death and axonal damage in the CNS [3], [4]. Thus, the pathogenesis of MS may be related to activation, migration and effector function of immune cells as well as their products such as cytokines, chemokines, adhesion molecules or other inflammatory factors [5]–[7]. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS [8].…”

Section: Introductionmentioning

confidence: 99%

Targeting the Shift from M1 to M2 Macrophages in Experimental Autoimmune Encephalomyelitis Mice Treated with Fasudil

et al. 2013

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We observed the therapeutic effect of Fasudil and explored its mechanisms in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Fasudil, a selective Rho kinase (ROCK) inhibitor, was injected intraperitoneally at 40 mg/kg/d in early and late stages of EAE induction. Fasudil ameliorated the clinical severity of EAE at different stages, and decreased the expression of ROCK-II in spleen, accompanied by an improvement in demyelination and inhibition of inflammatory cells. Fasudil mainly inhibited CD4+IL-17+ T cells in early treatment, but also elevated CD4+IL-10+ regulatory T cells and IL-10 production in late treatment. The treatment of Fasudil shifted inflammatory M1 to anti-inflammatory M2 macrophages in both early and late treatment, being shown by inhibiting CD16/32, iNOS, IL-12, TLR4 and CD40 and increasing CD206, Arg-1, IL-10 and CD14 in spleen. By using Western blot and immunohistochemistry, iNOS and Arg-1, as two most specific markers for M1 and M2, was inhibited or induced in splenic macrophages and spinal cords of EAE mice treated with Fasudil. In vitro experiments also indicate that Fasudil shifts M1 to M2 phenotype, which does not require the participation or auxiliary of other cells. The polarization of M2 macrophages was associated with the decrease of inflammatory cytokine IL-1β, TNF-α and MCP-1. These results demonstrate that Fasudil has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.

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The CD4+ T-cell subset lacking expression of the CD28 costimulatory molecule is expanded and shows a higher activation state in multiple sclerosis

Cited by 21 publications

References 51 publications

High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

Immunosenescence, Aging, and Systemic Lupus Erythematous

Targeting the Shift from M1 to M2 Macrophages in Experimental Autoimmune Encephalomyelitis Mice Treated with Fasudil

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