Reversal of T cell anergy in leprosy patients: in vitro presentation with Mycobacterium leprae antigens using murabutide and Trat peptide in liposomal delivery

Koduri, Sridevi; Khanna, Neena; Chattree, Vineeta; Pal, P. C.; Haq, W.; Rao, D. N.

doi:10.1016/s1567-5769(03)00181-4

Cited by 14 publications

(9 citation statements)

References 20 publications

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“…It can be hypothesized in the present study that IFN-g could be able to upregulate the expression of these costimulatory molecules on APC, although the levels were relatively low in unstimulated cells. In the same communication, we observed very low levels of IL-10 with the same formulation, however, there is an increased level of secretion of IL-10 when the PBMC were stimulated with M. leprae antigen alone in vitro [13]. This is in accordance with the observation that IL-10 is known to inhibit the upregulation of either CD80 or CD86 expression, while IFN-g increases the upregulation of these costimulatory molecules on human monocytemacrophages [17].…”

Section: Discussionsupporting

confidence: 84%

“…In one of the recent findings, IL-10 is shown to interfere with the proliferative response of gyT cells in lepromatous patients towards mycobacterial antigens [25]. Our study reported the restoration of T cell proliferative response using particulate mode of antigen delivery with decreased IL-10 levels followed by increased IFN-g levels [13]. Since there is not much variation in TCR gy in any of the group, TCR bearing ah had shown an increase during the in vitro stimulation with our formulation; it appears that liposomal presentation perhaps expand T cells bearing ah receptor.…”

Section: Discussionsupporting

confidence: 60%

“…Out of five mycobacterial antigens used, M. leprae total cell wall antigen (MLCWA) was proven the best antigen [13], and, hence, the same antigen under identical experimental conditions was used in the present study. All these antigens were provided by Dr. Patrick Brennan (Colorado State University, Colorado, USA) through WHO-IMMLEP/M.…”

Section: Antigensmentioning

confidence: 99%

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Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR αβ, TCR γδ) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and T cell peptide of Trat protein

Koduri

Khan

Keisham

et al. 2004

International Immunopharmacology

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 60%

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Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR αβ, TCR γδ) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and T cell peptide of Trat protein

Koduri

Khan

Keisham

et al. 2004

International Immunopharmacology

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“…Pathogen-specific T cell reactivity recovers after successful therapy in most cases with HIV infection, tuberculosis, and leprosy (31)(32)(33), whereas IRIS pathogenesis is considered to mainly occur in patients with high pathogen load (7,11,12). However, CWD IRIS supports the conclusion that pathogen-specific immune reconstitution is not a prerequisite for IRIS because: 1) CWD patients do not experience development of T. whipplei-specific T cell reactivity in peripheral blood before or after antimicrobial treatment; 2) pathogen-specific reactivity remains absent even at high T. whipplei burdens in tissues affected by IRIS; 3) IRIS affects the duodenal mucosa, the location of the major pathogen load in CWD, but also nongut loci; and 4) sites unaffected by IRIS reveal pathogen distribution comparable with adjacent tissue where IRIS manifests.…”

Section: Discussionmentioning

confidence: 99%

Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple’s Disease

Moos

Feurle

Schinnerling

et al. 2013

The Journal of Immunology

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During antimicrobial treatment of classic Whipple’s disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4+ T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3+, predominantly CD45RO+CD4+ T cells. In the periphery, initial reduction of CD4+ cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4+ T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4+ T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei–specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4+ T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

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“…In addition, in vitro treatment of T cells with murabutide, an MDP analog, reversed T cell anergy to mycobacteria leprae antigens (41) suggesting that in vivo the inability to mount an effective response to muramyl dipeptide may play a role in the exacerbation of the infection. Our findings, along with the fact that multibacillary leprosy is highly angiogenic (42), suggest that activation of the MDP pathway in vivo might be useful in the treatment of this disease.…”

Section: Discussionmentioning

confidence: 99%

Muramyl Dipeptide Induces Th17 Polarization through Activation of Endothelial Cells

Manni

Ding

Stohl

et al. 2011

The Journal of Immunology

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Endothelial cells (ECs) express the nucleotide-binding oligomerization domain (Nod) receptor 2, which recognizes the bacterial derivate muramyl dipeptide (MDP). MDP stimulation of these cells enhances their IL-6 production and may thus contribute to the immune and inflammatory activities in the skin. However, whether ECs are capable of influencing the development of T cell priming and its polarization remains unknown. We report that in vitro the murine bEnd.3 EC line induces, following MDP stimulation, a Th17 polarization at the expense of Th1 and Th2 polarization in the setting of Langerhans cell (LC) Ag presentation to responsive T cells as assessed by IL-17, IL-6, IFN-γ, and IL-4 production. Interestingly, IL-22 production, which has been associated with Th17 priming, was not influenced by MDP-treated bEnd.3 cells, illustrating differential regulation of this cytokine from IL-17. Additional analysis confirmed a significantly increased percentage of IL-17+CD4+ T cells by flow cytometry and an increased mRNA level of the specific Th17 transcription factor retinoic acid-related orphan receptor γt in cocultures of LCs and responsive T cells in the presence of activated bEnd.3 cells. Experiments using the RNA interference technique to knockdown IL-6 in bEnd.3 cells confirmed that IL-6 produced by bEnd.3 cells stimulated by MDP is at least partially involved in Th17 polarization. Our data suggest that activated ECs are capable of influencing LC Ag processing and presentation to T cells and induce a Th17 polarization. These results are important for the understanding of Th17-related disorders of the skin such as psoriasis.

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Reversal of T cell anergy in leprosy patients: in vitro presentation with Mycobacterium leprae antigens using murabutide and Trat peptide in liposomal delivery

Cited by 14 publications

References 20 publications

Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR αβ, TCR γδ) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and T cell peptide of Trat protein

Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR αβ, TCR γδ) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and T cell peptide of Trat protein

Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple’s Disease

Muramyl Dipeptide Induces Th17 Polarization through Activation of Endothelial Cells

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