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. 2012 Nov 1;8(11):1555-63.
doi: 10.4161/hv.22142. Epub 2012 Nov 1.

IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

Jiangmei Yin  1 , Anlan Dai, Tatiana Arango, Ravi S Kasinathan, Robert M Greenberg, Jean D Boyer
Affiliations

IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

Jiangmei Yin et al. Hum Vaccin Immunother. .

Abstract

The co-infection of HIV and helminth parasites, such as Schistosoma spp, has increased in sub-Saharan Africa. Many HIV vaccine candidate studies have been completed or are in ongoing clinical trials, but it is not clear how HIV vaccines might affect the course of schistosome infections. In this study, we immunized S. mansoni-infected mice with an efficient DNA vaccine that included HIV gag. Using this model, we found that Th2 cytokines, such as IL-4 and IL-13, were highly induced after schistosome infection. Treatment of infected mice with the HIV DNA vaccine resulted in a significant attenuation of this rise in IL-13 expression and an increase in expression of the Th1 cytokine, TNF-α. However, vaccine administration did not significantly influence the expression of IL-4, or IFN-γ, and did not affect T cell proliferative capacity. Interestingly, the IL-4 (+) IFN-γ (+) phenotype appears in schistosome-infected mice that received HIV vaccination, and is associated with the expression of transcription factors GATA3 (+) T-bet (+) in these mice. These studies indicate that DNA vaccination can have an impact on ongoing chronic infection.

Keywords: HIV vaccine; Th1 and Th2 responses; schistosome infection.

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Figures

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Figure 1. IL-13 expression one week after last immunization. Spleen lymphocytes were isolated one week after last immunization and SEA-specific IL-13 responses were assessed by standard ELISpot. Individual data of IL-13 producing cells after stimulation with SEA antigen for all mice are displayed. p < 0.05 per the unpaired t test.
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Figure 2. Th1 cytokine expression one week after last immunization. Fresh lymphocytes from all mice were isolated one week following the final immunization and analyzed for Th1 cytokines, TNFα, IFN-γ and IL-2. (A) Gating strategy shows TNFa, IFN-gamma and IL-2 from CD4+/CD8+ T cells. (B) Cytokines data for SEA (medium alone values subtracted) is enumerated per immunization group and shown for CD4+ and CD8+ T-cells. Data was acquired on an LSRI instrument analyzed with flowjo software. *p < 0.05 per the unpaired t test.
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Figure 3. Proliferative capacity of antigen-specific T-cells in infected and/or vaccinated animals. Lymphocytes from all mice were isolated one week following the final immunization and analyzed for proliferative capacity. (A) Gating strategy shows proliferative capacity from CD4+ or CD8+ T cells. (B) Proliferative data for SEA antigen (medium alone values subtracted) is enumerated per immunization group and shown for CD4+ and CD8+ T-cells. *p < 0.05 per the unpaired t test.
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Figure 4. The balance of Th1 and Th2 responses induced by schistosome infection and followed HIV vaccination. Lymphocytes isolated from one week after the last immunization were stimulated with antigen for 5 h and stained with surface and inner antibodies and analyzed by flow cytometry. (A) Expression of Th2 and Th1 cytokines, IL-4 and IFN-γ, in CD4+ T cells from one representative animal in each group. (B) Cytokine expression for antigen stimulation (medium alone values subtracted) is enumerated per immunization group and shown for IL-4, IFN-gamma and IFN-gamma+IL-4+. *p < 0.05 per the unpaired t test.
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Figure 5. Transcription factors, GATA-3 and T-bet, expression in mice with schistosome infection and followed HIV vaccination. Lymphocytes isolated from one week after last immunization were stimulated with antigen for 5 h and stained with surface and inner antibodies and analyzed by flow cytometry. (A) The expression of transcription factor GATA-3 and T-bet in CD4+ T cells from one representative mice in each group. (B) The transcription factors’ expression for antigen stimulation (medium alone values subtracted) is enumerated per immunization group and shown for GATA-3, T-bet and GATA-3+ T-bet+. *p < 0.05 per the unpaired t test.
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Figure 6. IL-10 regulated the balance of Th1 and Th2 induced by schistosome infection and followed HIV vaccination. Lymphocytes isolated from one week after last immunization were stimulated, stained, and analyzed by flow cytometry. IL-10 expression in CD4+ T cells is enumerated per immunization group. *p < 0.05 per the unpaired t test.
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