title: Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B, Acharya JC Bose Road, Kolkata, India.
authors.forename: Shibabrata
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B, Acharya JC Bose Road, Kolkata, India.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B, Acharya JC Bose Road, Kolkata, India.
authors.forename: Susmita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Dermatology, School of Tropical Medicine, Kolkata, India.
authors.forename: Joyashree N
authors.initials: JN
authors.lastname: Barbhuiya
authors.affiliation: Department of Dermatology, Calcutta Medical College, Kolkata, India.
authors.forename: Nilay K
authors.initials: NK
authors.lastname: Das
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B, Acharya JC Bose Road, Kolkata, India. ilatim@vsnl.net.
authors.forename: Mitali
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007194:India; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008297:Male; D012867:Skin / Q000276:immunology* / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D058408:Th1-Th2 Balance; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D018819:Dipeptidyl Peptidase 4
keywords: Adenosine deaminase activity; CD26; CD45RO; Post kala-azar dermal leishmaniasis; Soluble CD26