Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis
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.
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.
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.
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.
KeywordsAdenosine deaminase activity CD26 CD45RO Post kala-azar dermal leishmaniasis Soluble CD26
SM, MC, DM, and NKD designed the study; SM, DM, SG, JNB, and NKD performed the experiments, while MC, SM, and DM wrote the paper. The work received financial assistance from the Indian Council for Medical Research (ICMR), Council for Scientific & Industrial Research and the Department of Science and Technology (DST), Government of India. Senior Research Fellowships were provided by the INSPIRE Programme DST, Government of India to SM, while DM and SG were supported by the ICMR, Government of India.
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Conflicts of Interest
The authors report no conflicts of interest.
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