Enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in indian post-kala-azar dermal leishmaniasis

Sudipto Ganguly, Debanjan Mukhopadhyay, Nilay K. Das, Mehervani Chaduvula, Soumi Sadhu, Uttara Chatterjee, Mehebubar Rahman, Rama P. Goswami, Subhashish Kamal Guha, Dolanchampa Modak, Sudeshna Mallik, Debananda Gonju, Netai Pramanik, Joyashree N. Barbhuiya, Bibhuti Saha, Mitali Chatterjee

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1013-1022
Number of pages10
JournalJournal of Investigative Dermatology
Volume130
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Forkhead Transcription Factors
Leishmaniasis
Visceral Leishmaniasis
T-cells
Lymphocytes
Regulatory T-Lymphocytes
Interleukin-10
Skin
Leishmania donovani
CD28 Antigens
Cytokines
Antigens
Messenger RNA
Transcription factors
Flow cytometry
Biopsy
RNA-Directed DNA Polymerase
CD8 Antigens
Phytohemagglutinins
Pathology

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 journalArticle

Ganguly, S, Mukhopadhyay, D, Das, NK, Chaduvula, M, Sadhu, S, Chatterjee, U, Rahman, M, Goswami, RP, Guha, SK, Modak, D, Mallik, S, Gonju, D, Pramanik, N, Barbhuiya, JN, Saha, B & Chatterjee, M 2010, 'Enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in indian post-kala-azar dermal leishmaniasis', Journal of Investigative Dermatology, vol. 130, no. 4, pp. 1013-1022. https://doi.org/10.1038/jid.2009.393
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. / Enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in indian post-kala-azar dermal leishmaniasis. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 4. pp. 1013-1022.
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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.",
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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

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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.

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