Abstract
Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. Insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. In patients with PKDL (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative responses using flow cytometry. In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines (IFN-γ and IL-10) and the T-regulatory transcription factor forkhead box protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with PKDL, circulating CD8+ CD28- and antigen-induced IL-10+ CD3+ lymphocytes were increased and receded with treatment. CD8 lymphocytes showed impaired proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin, which were reinstated after treatment. At presentation, the upregulated lesional IFN-γ and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed after treatment. In Indian patients with PKDL, increased frequency of the CD8+ CD28 - phenotype, enhanced antigen-specific IL-10 production, and accompanying anergy of circulating lymphocytes suggest their regulatory nature. Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests their possible recruitment into the lesional site, which would sustain disease pathology.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1013-1022 |
| Number of pages | 10 |
| Journal | Journal of Investigative Dermatology |
| Volume | 130 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in indian post-kala-azar dermal leishmaniasis. / Ganguly, Sudipto; Mukhopadhyay, Debanjan; Das, Nilay K.; Chaduvula, Mehervani; Sadhu, Soumi; Chatterjee, Uttara; Rahman, Mehebubar; Goswami, Rama P.; Guha, Subhashish Kamal; Modak, Dolanchampa; Mallik, Sudeshna; Gonju, Debananda; Pramanik, Netai; Barbhuiya, Joyashree N.; Saha, Bibhuti; Chatterjee, Mitali.
In: Journal of Investigative Dermatology, Vol. 130, No. 4, 04.2010, p. 1013-1022.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in indian post-kala-azar dermal leishmaniasis
AU - Ganguly, Sudipto
AU - Mukhopadhyay, Debanjan
AU - Das, Nilay K.
AU - Chaduvula, Mehervani
AU - Sadhu, Soumi
AU - Chatterjee, Uttara
AU - Rahman, Mehebubar
AU - Goswami, Rama P.
AU - Guha, Subhashish Kamal
AU - Modak, Dolanchampa
AU - Mallik, Sudeshna
AU - Gonju, Debananda
AU - Pramanik, Netai
AU - Barbhuiya, Joyashree N.
AU - Saha, Bibhuti
AU - Chatterjee, Mitali
PY - 2010/4
Y1 - 2010/4
N2 - Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. Insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. In patients with PKDL (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative responses using flow cytometry. In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines (IFN-γ and IL-10) and the T-regulatory transcription factor forkhead box protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with PKDL, circulating CD8+ CD28- and antigen-induced IL-10+ CD3+ lymphocytes were increased and receded with treatment. CD8 lymphocytes showed impaired proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin, which were reinstated after treatment. At presentation, the upregulated lesional IFN-γ and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed after treatment. In Indian patients with PKDL, increased frequency of the CD8+ CD28 - phenotype, enhanced antigen-specific IL-10 production, and accompanying anergy of circulating lymphocytes suggest their regulatory nature. Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests their possible recruitment into the lesional site, which would sustain disease pathology.
AB - Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. Insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. In patients with PKDL (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative responses using flow cytometry. In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines (IFN-γ and IL-10) and the T-regulatory transcription factor forkhead box protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with PKDL, circulating CD8+ CD28- and antigen-induced IL-10+ CD3+ lymphocytes were increased and receded with treatment. CD8 lymphocytes showed impaired proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin, which were reinstated after treatment. At presentation, the upregulated lesional IFN-γ and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed after treatment. In Indian patients with PKDL, increased frequency of the CD8+ CD28 - phenotype, enhanced antigen-specific IL-10 production, and accompanying anergy of circulating lymphocytes suggest their regulatory nature. Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests their possible recruitment into the lesional site, which would sustain disease pathology.
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U2 - 10.1038/jid.2009.393
DO - 10.1038/jid.2009.393
M3 - Article
C2 - 20032994
AN - SCOPUS:77949539652
VL - 130
SP - 1013
EP - 1022
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 4
ER -