Dichotomy of protective cellular immune responses to human visceral leishmaniasis


Khalil, EAG; Ayed, NB; Musa, AM; Ibrahim, ME; Mukhtar, MM; Zijlstra, EE; Elhassan, IM; Smith, PG; Kieny, PM; Ghalib, HW; Zicker, F; Modabber, F; Elhassan, AM; (2005) Dichotomy of protective cellular immune responses to human visceral leishmaniasis. Clinical and experimental immunology, 140 (2). p. 349. ISSN 0009-9104 DOI: 10.1111/j.1365-2249.2005.02768.x

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Abstract

Healing/protective responses in human visceral leishmaniasis (VL) are associated with stimulation/production of Th1 cytokines, such as interferon IFN-gamma, and conversion in the leishmanin skin test (LST). Such responses were studied for 90 days in 44 adult healthy volunteers from VL non-endemic areas, with no past history of VL/cutaneous leishmaniasis (CL) and LST non-reactivity following injection with one of four doses of Alum-precipitated autoclaved Leishmania major (Alum/ALM) +/- bacille Calmette-Guerin (BCG), a VL candidate vaccine. The vaccine was well tolerated with minimal localized side-effects and without an increase in antileishmanial antibodies or interleukin (IL)-5. Five volunteers (5/44; 11.4%) had significant IFN-gamma production by peripheral blood mononuclear cells (PBMCs) in response to Leishmania antigens in their prevaccination samples (P = 0.001) but were LST non- reactive. On day 45, more than half the volunteers (26/44; 59.0%) had significantly high LST indurations (mean 9.2 +/- 2.7 mm) and high IFN-gamma levels (mean 1008 +/- 395; median 1247 pg/ml). Five volunteers had significant L. donovani antigen- induced IFN-gamma production (mean 873 +/- 290; median 902; P = 0.001), but were non-reactive in LST. An additional five volunteers (5/44; 11.4%) had low IFN-gamma levels (mean 110 +/- 124 pg/ml; median 80) and were non-reactive in LST (induration = 00 mm). The remaining eight volunteers had low IFN-gamma levels, but significant LST induration (mean 10 +/- 2.9 mm; median 11). By day 90 the majority of volunteers (27/44; 61.4%) had significant LST induration (mean 10.8 +/- 9.9 mm; P < 0.001), but low levels of L. donovani antigen-induced IFN-gamma (mean 66.0 +/- 62 pg/ml; P > 0.05). Eleven volunteers (11/44; 25%) had significantly high levels of IFN-gamma and LST induration, while five volunteers had low levels of IFN-gamma (< 100 pg/ml) and no LST reactivity (00 mm). One volunteer was lost to follow-up. In conclusion, it is hypothesized that cellular immune responses to human VL are dichotomatous, and that IFN-gamma production and the LST response are not in a causal relationship. Following vaccination and probably cure of VL infection, the IFN-gamma response declines with time while the LST response persists. LST is a simple test that can be used to assess candidate vaccine efficacy.

Item Type: Article
Keywords: dichotomy, human visceral leishmaniasis, immune responses, Azar dermal leishmaniasis, major plus bcg, kala-azar, cutaneous, leishmaniasis, eastern sudan, t-cell, healthy-volunteers, controlled-trial, double-blind, donovani, Adult, Animals, Antibodies, Protozoan, biosynthesis, Antigens, Protozoan, immunology, Dose-Response Relationship, Immunologic, Female, Follow-Up Studies, Humans, Immunity, Cellular, Immunoglobulin G, biosynthesis, Interferon Type II, biosynthesis, Interleukin-5, biosynthesis, Leishmania donovani, immunology, Leishmania major, immunology, Leishmaniasis, Visceral, immunology, prevention & control, Male, Mycobacterium bovis, immunology, Protozoan Vaccines, immunology, Research Support, Non-U.S. Gov't, Skin Tests
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Leishmaniasis Group
Centre for Global Non-Communicable Diseases (NCDs)
Neglected Tropical Diseases Network
PubMed ID: 15807861
Web of Science ID: 227968900020
URI: http://researchonline.lshtm.ac.uk/id/eprint/13669

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