Cellular Profile of Cytokine Production in a Patient with Visceral Leishmaniasis: γδ⁺ T Cells Express Both Type 1 Cytokines and Interleukin‐10

Abstract

The cytokine profile of CD4 , CD8 T cells, gd T cells and natural killer (NK) cells (CD94 CD3 ± ) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus-negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon-g (IFN-g), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13 and tumour necrosis factor (TNF)-a expression in peripheral blood mononuclear cells stimulated with phorbol 12-myristate 13-acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4 cells were identified as major cytokine-expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL-4-and IL-13-expressing CD8 cells was noted. NK cells and gd T cells, thought to be involved in innate host defences against Leishmania, expressed IFN-g and TNF-a. Ten per cent of gd T cells expressed IL-10, predominantly together with IFN-g, suggesting additional immune-regulatory roles for this T-cell subset in VL.

Cryptosporidium parvum-Specific CD4 Th1 Cells from Sensitized Donors Responding to Both Fractionated and Recombinant Antigenic Proteins

“…2), is consistent with the hypothesis that ␥/␦ T cells are involved in the early stage of C. parvum infection; in fact, the role of ␥/␦ T cells as effector cells early in the immune response has been shown for a wide variety of infectious agents (24,30). Moreover, in a murine model of C. parvum infection, ␥/␦ T cells have been shown to contribute to controlling the infection in the early stages (9,44).…”

Disparate Immunoregulatory Potentials for Double-Negative (CD4−CD8−) αβ and γδ T Cells from Human Patients with Cutaneous Leishmaniasis

“…However, this subpopulation was also highly committed toward IL-10 production, suggesting a modulatory role of ␥␦ T cells during visceral leishmaniasis (18). IL-10 has been associated with susceptibility to L. donovani infection in mice and humans (16,23) but has also been related to prevention of pathology due to exacerbated Th1 responses triggered by the Leishmania during the cutaneous form of the disease (3).…”

Immunostimulatory Properties of Dendritic Cells after Leishmania donovani Infection Using an In Vitro Model of Liver Microenvironment

“…Furthermore, L. donovani infection of DCs differentiated in RLEC-CM restored their impaired capacity to stimulate allogeneic lymphocyte proliferation and up-regulated lymphocyte IFNγ secretion. A similar simultaneous co-expression of IL-10 and IFNγ is detected in the serum of acute VL patients [37], [38]. Furthermore, a Leishmania -specific subtype of CD4+ lymphocytes from individuals cured of VL has even been described as IFNγ+/IL-10+ [39].…”

“…Thus, infected hepatic DCs may be partly responsible for the high serum IL-10 levels observed in patients with active VL [37], [38]. Furthermore, L. donovani infection of DCs differentiated in RLEC-CM restored their impaired capacity to stimulate allogeneic lymphocyte proliferation and up-regulated lymphocyte IFNγ secretion.…”