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01-01-2016 | Original Article

Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis

Authors: Shibabrata Mukherjee, Debanjan Mukhopadhyay, Susmita Ghosh, Joyashree N. Barbhuiya, Nilay K. Das, Mitali Chatterjee

Published in: Journal of Clinical Immunology | Issue 1/2016

Abstract

Purpose

Leishmania, the causative organisms for leishmaniasis, reside in host macrophages and survive by modulating the microbicidal pathways via attenuation of the oxidative burst and/or suppression of cell-mediated immunity. As post kala-azar dermal leishmaniasis (PKDL), the dermal sequela of visceral leishmaniasis, has no animal model, the underlying mechanism(s) that nullify the microbicidal effector mechanisms remain poorly understood. This study was aimed at assessing the status of dipeptidyl peptidase CD26, a co-stimulatory molecule that is essential for T-cell signal activation.

Methods

The frequency/expression of CD26 and CD45RO/RA was evaluated by flow cytometry, while levels of soluble CD26 (sCD26), CXCL-10, RANTES, IL-10 and TGF-β along with adenosine deaminase (ADA) activity were measured using ELISA.

Results

In patients with PKDL vis-à-vis healthy individuals, there was a significant decrease in the frequency and expression of CD26 on CD3⁺CD8⁺ T-cells, which was accompanied by a significant lowering of plasma levels of sCD26. Furthermore, these patients showed a significant decrease in the frequency of CD45RO⁺/CD8⁺ T-cells, concomitant with a significant increase in the proportion of CD45RA⁺/CD8⁺ T-cells. This could collectively translate into reduced formation of the immunological synapse of CD26, CD45RO, and ADA, and lead to an attenuation of the Th1 responses. The decreased levels of CD26 and sCD26 correlated negatively with raised levels of Th2 cytokines, IL-10, and TGF-β along with the lesional parasite load, indicating disease specificity.

Conclusions

Taken together, the decreased expression and secretion of CD26 in patients with PKDL resulted in impairment of the CD26-ADA interaction, and thereby possibly contributed to T-cell unresponsiveness, emphasizing the need to develop immunomodulatory therapies against PKDL and by extension, the leishmaniases.

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Title: Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis
Authors: Shibabrata Mukherjee
Debanjan Mukhopadhyay
Susmita Ghosh
Joyashree N. Barbhuiya
Nilay K. Das
Mitali Chatterjee
Publication date: 01-01-2016
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 1/2016
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-015-0215-8

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Abstract

Purpose

Methods

Results

Conclusions

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