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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes
D W Beno1, A G Stöver, H L Mathews
1Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.
Insights
CD8+ T lymphocytes activated by IL-2 effectively inhibit Candida albicans hyphae growth. Natural killer (NK) cells, activated by IL-2 or IFN-gamma, showed minimal antifungal activity against hyphae.
Area of Science:
- Immunology
- Mycology
Background:
- Interleukin-2 (IL-2) activated splenocytes previously demonstrated inhibition of Candida albicans hyphae.
- The specific lymphocyte subset mediating this antifungal activity remained to be identified.
Purpose of the Study:
- To identify the specific lymphocyte subset responsible for the antifungal activity against Candida albicans hyphae.
- To elucidate the role of CD8+ T cells and NK1.1+ cells in IL-2-mediated antifungal responses.
Main Methods:
- Enrichment and depletion of CD8+ and NK1.1+ cells from IL-2-activated lymphocyte populations.
- Assays for antifungal activity against Candida albicans hyphae.
- Cytotoxic activity assays against NK-resistant and NK-sensitive cell lines.
Main Results:
- Plastic nonadherent CD8+ lymphocytes were identified as the primary mediators of antifungal activity against C. albicans hyphae.
- Enrichment of CD8+ cells enhanced both antifungal and cytotoxic activity, while depletion reduced it.
- NK1.1+ cells showed reduced antifungal activity against hyphae but increased cytotoxicity against NK-sensitive cells.
- Antifungal lymphocyte generation required IL-2, and IFN-gamma could not substitute for IL-2.
Conclusions:
- IL-2-activated CD8+ T lymphocytes are the main effectors against the hyphal form of C. albicans.
- IL-2- or IFN-gamma-activated NK cells exhibit limited or no antifungal activity against C. albicans hyphae.
Abstract:
We have shown previously that IL-2-activated splenocytes can inhibit the growth of Candida albicans hyphae in vitro. Herein we demonstrate that plastic nonadherent lymphocytes that are CD8+ mediate the antifungal activity. Enrichment for CD8+ cells markedly enhanced the antifungal activity of the IL-2-activated lymphocyte population for C. albicans and the cytotoxic activity of the lymphocytes for an NK-resistant cell line. Depletion of CD8+ cells reduced the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line. Enrichment for NK1.1+ cells markedly reduced the antifungal activity of the lymphocyte population for C. albicans and increased the cytotoxic activity of the lymphocytes for an NK-sensitive cell line. Depletion of NK1.1+ cells increased the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line. Generation of the antifungal lymphocytes in culture required IL-2 and was not replaced with IFN-gamma. These data show that IL-2-activated CD8+ T lymphocytes exert the greatest amount of antifungal effect against the hyphal form of C. albicans, whereas IL-2- or IFN-gamma-activated NK cells have little or no effect against the hyphae.
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