Detection of early apoptosis and cell death in T CD4+ and CD8+ cells from lesions of patients with localized cutaneous leishmaniasis

Abstract

Human localized cutaneous leishmaniasis (LCL), induced by Leishmania braziliensis, ranges from a clinically mild, self-healing disease with localized cutaneous lesions to severe forms which can present secondary metastatic lesions. The T cell-mediated immune response is extremely important to define the outcome of the disease; however, the underlying mechanisms involved are not fully understood. A flow cytometric analysis of incorporation of 7-amino actinomycin D and CD4 + or CD8 + T cell surface phenotyping was used to determine whether different frequencies of early apoptosis or accidental cell death occur at different stages of LCL lesions. When all cells obtained from a biopsy sample were analyzed, larger numbers of early apoptotic and dead cells were observed in lesions from patients with active disease (mean = 39.5 ± 2.7%) as compared with lesions undergoing spontaneous healing (mean = 17.8 ± 2.2%). Cells displaying normal viability patterns obtained from active LCL lesions showed higher numbers of early apoptotic events among CD8 + than among CD4 + T cells (mean = 28.5 ± 3.8 and 15.3 ± 3.0%, respectively). The higher frequency of cell death events in CD8 + T cells from patients with LCL may be associated with an active form of the disease. In addition, low frequencies of early apoptotic events among the CD8 + T cells were observed in two patients with self-healing lesions. Although the number of patients in the latter group was small, it is possible to speculate that, during the immune response, differences in apoptotic events in CD4 + and CD8 + T cell subsets could be responsible for controlling the CD4/CD8 ratio, thus leading to healing or maintenance of disease. Correspondence

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

“…Plasmodium species, including Plasmodium falciparum and Plasmodium berghei induce Fas-Fas ligand-mediated apoptosis in various host immune cells [36][37][38][39]. Moreover, apoptotic induction has been reported in Cryptosporidium parvum infected-biliary and intestinal epithelial cells [40][41][42][43], Leishmania donovani-infected splenic CD4 T cells, Leishmania braziliensis-infected CD4 and CD8 T cells [44], Plasmodium sporozoiteinfected Kupffer cells apoptosis [45], to escape the host defense systems. One reason why Plasmodium berghei -infected hepatocytes become resistant to apoptosis is the activation of hepatocyte growth factor receptor (HGF), which binds receptor tyrosine kinase MET and results in hepatocyte proliferation, survival and contribute to transmission success [46,47].…”

The Contribution of the Fas/FasL Apoptotic Pathway in Ulcer Formation during Leishmania major-Induced Cutaneous Leishmaniasis

“…16 However, low levels of FasL-expressing cells have been reported in skin biopsies from L. aethiopicainduced local and diffuse CL. 17 We propose that ulceration during L. major-induced CL is caused by FasL-expressing Leishmania-primed T cells and macrophages, through induction of apoptosis in Fasexpressing keratinocytes.…”

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

“…Por el contrario, las lesiones de personas con curación espontánea mostraron muy bajo porcentaje de células T CD8 + en apoptosis. 47 De manera adicional, se describió un alto porcentaje de linfocitos T CD8 + reactivos a Leishmania en los infiltrados inflamatorios y bajo porcentaje en sangre. 44 De modo conjunto, estos hallazgos demuestran que los linfocitos T CD8 + participan de forma activa y promueven la curación.…”