Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile

Abstract

In Sudan, post kala‐azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala‐azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined the immunological response in lesions of PKDL patients by immunohistochemistry and compared the findings with results obtained using peripheral blood mononuclear cells (PBMCs). In all lesions, parasites or parasite antigen were present and provoked the formation of an inflammatory infiltrate consisting of a mixture of macrophages, lymphocytes, and plasma cells. In patients who had high interferon‐gamma (IFNγ) responses to Leishmania antigen in vitro, compact epithelioid granulomas were formed. The inflammatory cells were mainly CD3+ and interleukin‐10 (IL10) was the most prominent cytokine in the lesions. However, IFNγ was found in all and IL4 in most lesions, in varying amounts. PBMCs from all patients responded to Leishmania antigen by IFNγ production or proliferation. The results indicate that PKDL develops as a result of an influx of immunocompetent cells into skin, which harbours parasites. The inflammatory response to the parasites is complex. It involves several cell types and cytokines, of which some are antagonistic. It is conceivable that the balance between these cytokines determines the outcome of the disease. Copyright © 1999 John Wiley & Sons, Ltd.

Disseminated Cutaneous Leishmaniasis Resembling Post-Kala-Azar Dermal Leishmaniasis Caused by Leishmania donovani in Three Patients Co-Infected with Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Ethiopia

“…27,[44][45][46][47][48][49] In our patients, we observed consistently low CD4 cell counts and high parasitic loads in splenic and bone marrow aspirates and skin lesions, which suggestes that immunosuppression enables the parasites to multiply in the periphery. Therefore, we prefer to consider the cases described herein as cutaneous dissemination of visceral disease.…”

Clinical and Immunological Aspects of Post–Kala-Azar Dermal Leishmaniasis in Bangladesh

“…For PKDL without visceral involvement, the systemic cytokine response may be a relatively poor reflection of local skin responses. 26,29 Studies in affected dermis show mRNA for IFNγ, IL-6 and −10, and TNFα 26 and positive immunohistochemical staining for IFNγ and IL-10 and −4.…”

Multiplex analysis of circulating cytokines in the sera of patients with different clinical forms of visceral leishmaniasis

“…One patient also had circulating IL-6 and IFN-g while the other had accompanying IL-2 activity. In a study evaluating PKDL in Sudanese patients, researchers found IFN-g and IL-10 in 100% (6/6) and IL-4 in 83% (5/6) of the inflammatory infiltrates from lesion biopsy samples, although these were the only cytokines that were tested (27). After stimulation of peripheral blood mononuclear cells with LDP (crude soluble promastigote antigen), these researchers reported that the IL-10 and IFN-g were found primarily among CD41 T cells using intracellular cytokine staining.…”