Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis.
BACKGROUND
Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined.


METHODS
Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses.


RESULTS
Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10.


CONCLUSIONS
IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.
Ganguly
Sudipto
S
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
Das
Nilay Kanti
NK
Panja
Moumita
M
Pal
Shekhar
S
Modak
Dolanchampa
D
Rahaman
Mehebubar
M
Mallik
Sudeshna
S
Guha
Subhashis Kamal
SK
Pramanik
Netai
N
Goswami
Ramapada
R
Barbhuiya
Joyashree Nath
JN
Saha
Bibhuti
B
Chatterjee
Mitali
M
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood*; D007194:India / Q000453:epidemiology; D016753:Interleukin-10 / Q000097:blood*; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000150:complications* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D017252:CD3 Complex; D007074:Immunoglobulin G; D016753:Interleukin-10