Regulatory T-Cells: Diverse Phenotypes Integral to Immune Homeostasis and Suppression

GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Toxicologic Pathology (Impact Factor: 2.14). 01/2012; 40(2):186-204. DOI: 10.1177/0192623311430693
Source: PubMed


Regulatory T-cells (T(REG)) are diverse populations of lymphocytes that regulate the adaptive immune response in higher vertebrates. T(REG) delete autoreactive T-cells, induce tolerance, and dampen inflammation. T(REG) cell deficiency in humans (i.e., IPEX [Immunodysregulation, Polyendocrinopathy and Enteropathy, X-linked syndrome]) and animal models (e.g., "Scurfy" mouse) is associated with multisystemic autoimmune disease. T(REG) in humans and laboratory animal species are similar in type and regulatory function. A molecular marker of and the cell lineage specification factor for T(REG) is FOXP3, a forkhead box transcription factor. CD4(+) T(REG) are either natural (nT(REG)), which are thymus-derived CD4(+)CD25(+)FOXP3(+) T-cells, or inducible (i.e., Tr1 cells that secrete IL-10, Th3 cells that secrete TGF-β and IL-10, and Foxp3(+) Treg). The proinflammatory Th17 subset has been a major focus of research. T(H)17 CD4(+) effector T-cells secrete IL-17, IL-21, and IL-22 in autoimmune and inflammatory disease, and are dynamically balanced with T(REG) cell development. Other lymphocyte subsets with regulatory function include: inducible CD8(+) T(REG), CD3(+)CD4(-)CD8(-) T(REG) (double-negative), CD4(+)Vα14(+) (NKT(REG)), and γδ T-cells. T(REG) have four regulatory modes of action: secretion of inhibitory cytokines (e.g., IL-10 and TGF-β), granzyme-perforin-induced apoptosis of effector lymphocytes, depriving effector T-cells of cytokines leading to apoptosis, or inhibition of dendritic cell function. The role of T(REG) in mucosal sites, inflammation/infection, pregnancy, and cancer as well as a review of T(REG) as a modulatory target in drug development will be covered.

Download full-text


Available from: Richard A Peterson, Oct 20, 2014
  • Source
    • "Studies on Treg and SLE are controversial [7], however most studies have shown reduced numbers of Treg in active disease [31]. CD4 + CD25 high Fox- p3 + Treg subset is referred as tTreg, which are thymus-derived, highly dependent on IL-2 for their development, function, and homeostasis [8], and plays an essential role in prevention of autoimmunity and exacerbated immune responses [32]. Studies have reported that antigen stimulation and chronic inflammation may lead to CD4 + CD25 À cells to differentiate in CD4 + CD25 + FOXP3 + Treg at the periphery, by activating Foxp3 [33] [34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis.Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.
    Full-text · Article · Dec 2015 · Human immunology
  • Source
    • "Treg cells are a subset of CD4 + T-cells that are specialized for suppressive function. Treg cells differentiate from na¨ıve CD4 + T-cells in presence of soluble factors such as IL-10 and TGF-í µí»½ [13] [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4 + T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF- β subset of CD4 + CD25 + CD127 − Treg cells, which overexpressed LAP TGF- β . This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF- β subset of CD4 + CD25 + CD127 − Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.
    Full-text · Article · Nov 2015
  • Source
    • "Even T-reg response to quercetin could be a fine marker to probe the inflammatory injury due to heat stress, particularly because regulatory T cells need more time than the chemical activity on intracellular enzymatic and signaling systems needs. Furthermore, they modulate immune downregulation; therefore, T cells are proving to be reliable hallmarks of a balanced response to stressors [8]. The authors limited their testing to immune markers such as inflammatory cytokines, but it would be very interesting to also assay T-reg– derived cytokines in plasma samples. "

    Full-text · Article · Feb 2015 · Nutrition Research
Show more