Regulation of myeloperoxidase-specific T cell responses during disease remission in antineutrophil cytoplasmic antibody-associated vasculitis: The role of Treg cells and tryptophan degradation

Candida albicansis an opportunistic fungal pathogen that normally exists as a harmless commensal in humans. In instances where host debilitation occurs,Candidacan cause a range of clinical infections, and whilst these are primarily superficial, effecting mucosal membranes, systemic infections can develop in severely immunocompromised individuals. The mechanism of host immunity during commensal carriage ofC. albicanshas been intensively studied. In this paper, we present the most recent information concerning host recognition ofC. albicansleading to cytokine production and the subsequent T-cell responses generated in response toC. albicans. Particular focus is given to the role of the IL-12 cytokine family including IL-12, IL-23, IL-27, and IL-35, in host immunity toCandida. T-cells are considered crucial in the regulation of immunity and inflammation. In this regard, the role of Th1/2, helper cells, together with the recently identified Th17 and Treg cells in candidosis will be discussed. Understanding the detailed mechanisms that underlie host immunity toCandidanot only will be of benefit in terms of the infections caused by this organism but could also be exploited in the development of therapeutic interventions for other diseases.

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Dysfunctional T Regulatory Cells in Myeloma: Molecular Mechanisms of Dysregulation.

Blood ◽

10.1182/blood.v106.11.3462.3462 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3462-3462

Author(s):

Rao H. Prabhala ◽

Paola Neri ◽

Pierfrancesco Tassone ◽

Jooeun E. Bae ◽

Masood A. Shammas ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Treg Cell ◽

Cell Function ◽

Cell Activity ◽

T Cell Responses ◽

Treg Cells ◽

Cell Responses ◽

Treg Cell Function

Abstract Multiple myeloma (MM) is characterized by production of monoclonal immunoglobulin, associated with suppressed uninvolved immunoglobulins and dysfunctional T cell responses. The biological basis of this dysfunction remains ill defined. Since T regulatory (Treg) cells play an important role in suppressing normal immune responses, we have here evaluated the potential role of Treg cells in immune dysfunction in MM. We observed a significant increase in CD4+CD25+ T cells in individuals with monoclonal gammopathy of undetermined significance (MGUS) and patients with MM compared to normal donors (25% and 26% versus 14%, respectively); however, Treg cells as measured by Foxp3 expression are significantly decreased in both MGUS (1.6±0.5%, p<0.01) and MM (1.6±0.5%, p<0.01) compared to normal donors (6.0±0.8%). Additionally, these Treg cells also do not function normally. Treg cells from patients with MM and MGUS even when added in higher proportions are unable to suppress anti-CD3-mediated T cell proliferation. This decreased number and function of Treg cells in MGUS and in MM may account, at least in part, for the non-specific increase in CD4+CD25+ T cells, thereby contributing to dysfunctional T cell responses. We have further analyzed the molecular basis for the Treg cell dysfunction in myeloma. Based on the preliminary results suggesting a role of IL-6 in Treg cell function and since both serum IL-6 and soluble IL-6 receptor levels are significantly elevated in MGUS and MM, we evaluated the role of IL-6 and its soluble receptor on Treg cell function. We observed that the addition of IL-6 and/or sIL-6 receptor to the culture leads to loss of Treg cell activity in normal donor cells similar to one observed in myeloma patients; and conversely, when Treg cells from MM patients are treated with the anti-IL-6 antibody or IL-6 receptor super antagonist, sant 7, the suppressive activity of Treg cells is restored. Additionally, we have preliminary evidence of expansion of Foxp3+ cell numbers in PBMC from MM patients following in vitro treatment with anti-IL-6 antibody. This data suggests a role of IL-6 and bone marrow microenvironment in dysfunctional Treg cells in MM and that inhibition of IL-6 signaling results in beneficial effects on T cell activity by increasing Treg cell activity. A blockade of IL-6 signaling thus emerges as a potential approach to establish immune homeostasis to improve immune function in MM.

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Faculty Opinions recommendation of Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1047136.498191 ◽

2006 ◽

Author(s):

Kendall Smith

Keyword(s):

T Cell ◽

Rhesus Macaques ◽

T Cell Responses ◽

Cd8 T Cell ◽

Vaccine Regimen ◽

Cell Responses ◽

Protein Boost ◽

Boost Vaccine

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Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations

International Immunology ◽

10.1093/intimm/13.12.1583 ◽

2001 ◽

Vol 13 (12) ◽

pp. 1583-1593 ◽

Cited By ~ 113

Author(s):

Amariliz Rivera ◽

Chiann-Chyi Chen ◽

Naomi Ron ◽

Joseph P. Dougherty ◽

Yacov Ron

Keyword(s):

T Cell ◽

B Cells ◽

Lymph Nodes ◽

Cell Expansion ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cell Responses ◽

Antigen Presenting

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Assessment of CD4+ T Cell Responses to Glutamic Acid Decarboxylase 65 Using DQ8 Tetramers Reveals a Pathogenic Role of GAD65 121–140 and GAD65 250–266 in T1D Development

PLoS ONE ◽

10.1371/journal.pone.0112882 ◽

2014 ◽

Vol 9 (11) ◽

pp. e112882 ◽

Cited By ~ 21

Author(s):

I-Ting Chow ◽

Junbao Yang ◽

Theresa J. Gates ◽

Eddie A. James ◽

Duy T. Mai ◽

...

Keyword(s):

T Cell ◽

Glutamic Acid ◽

Glutamic Acid Decarboxylase ◽

T Cell Responses ◽

Cd4 T Cell ◽

Acid Decarboxylase ◽

Pathogenic Role ◽

Cell Responses ◽

Glutamic Acid Decarboxylase 65

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PD-L1 – PD-1 interactions limit effector Treg cell populations at homeostasis and during infection

10.1101/2020.12.09.416990 ◽

2020 ◽

Author(s):

J.A. Perry ◽

J.T. Clark ◽

J. Gullicksrud ◽

J. DeLong ◽

L. Shallberg ◽

...

Keyword(s):

T Cell ◽

Treg Cell ◽

Cell Activity ◽

T Cell Responses ◽

Treg Cells ◽

Whole Body ◽

Cell Responses ◽

Early Production ◽

Ifn Γ ◽

Specific Deletion

AbstractWhile much is known about the factors that promote the development of diverse Treg cell responses, less is known about the pathways that constrain Treg cell activities. The studies presented here reveal that at homeostasis there is a population of effector Treg cells that express PD-1, and that blockade of PD-L1 or loss of PD-1 results in increased Treg cell activity. In response to infection with the parasite T. gondii, the early production of IFN-γ results in widespread upregulation of PD-L1. Moreover, blockade of PD-L1, whole body deletion of PD-1, or lineage-specific deletion of PD-1 in Foxp3+ cells prevented the loss of the effector Treg cells but resulted in reduced pathogen specific CD4+ T cell responses during infection. Thus, at homeostasis basal PD-L1 expression constrains and tunes the pool of Treg cells, but during infection the upregulation of PD-L1 provides a mechanism to contract the Treg cell population required to maximize the development of pathogen specific CD4+ T cell responses.

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Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex.

Journal of Experimental Medicine ◽

10.1084/jem.149.1.150 ◽

1979 ◽

Vol 149 (1) ◽

pp. 150-157 ◽

Cited By ~ 56

Author(s):

P C Doherty ◽

J C Bennink

Keyword(s):

T Cells ◽

T Cell ◽

Vaccinia Virus ◽

T Cell Responses ◽

Cytotoxic T Cell ◽

Cell Responses ◽

Antigen Complex ◽

Infected Cells ◽

Cytotoxic T Cell Responses

BALB/c (H-2Kd-Dd) spleen and lymph node populations were specifically depleted of alloreactive potential by filtration through H-2 different, irradiated recipients. These negatively selected T cells were then stimulated with vaccinia virus in mice expressing the foreign H-2 determinants encountered previously in the filter environment. Strong virus-immune cytotoxic T-cell responses were seen in the context of H-2Kk and H-2Ks, but not 2H-2Kb. The T cells generated were not cross-reactive for the H-2Kk and H-2Kd alleles, and responsiveness was independent of concurrent presence of effector populations operating at H-2D. These findings are consisent with the idea that recognition is mediated via a complex receptor, part of which is specific for virus and part for self H-2. The capacity to interact with allogeneic, virus-infected cells may then reflect aberrant recognition of a virus-H-2-antigen complex by this single, large binding site. For instance, the T cell which would normally recognize H-2Kd-virus x, or H-2Dd-minor histocompatibility antigen Z, may now show specificity for H-2Kk-vaccinia virus. Implications for both the selective role of the thymus and for mechanisms of tolerance are discussed.

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