NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen

Ramakrishna Vankayalapati, Peter Klucar, Benjamin Wizel, Stephen Weis, Buka Samten, Hassan Safi, Homayoun Shams, Peter F. Barnes

Research output: Contribution to journalArticleResearchpeer-review

122 Citations (Scopus)

Abstract

We studied the role of NK cells in regulating human CD8+ T cell effector function against mononuclear phagocytes infected with the intracellular pathogen Mycobacterium tuberculosis. Depletion of NK cells from PBMC of healthy tuberculin reactors reduced the frequency of M. tuberculosis-responsive CD8+IFN-γ+ cells and decreased their capacity to lyse M. tuberculosis-infected monocytes. The frequency of CD8+IFN-γ+ cells was restored by soluble factors produced by activated NK cells and was dependent on IFN-γ, IL-15, and IL-18. M. tuberculosis-activated NK cells produced IFN-γ, activated NK cells stimulated infected monocytes to produce IL-15 and IL-18, and production of IL-15 and IL-18 were inhibited by anti-IFN-γ. These findings suggest that NK cells maintain the frequency of M. tuberculosis-responsive CD8+IFN-γ+ T cells by producing IFN-γ, which elicits secretion of IL-15 and IL-18 by monocytes. These monokines in turn favor expansion of Tc1 CD8+ T cells. The capacity of NK cells to prime CD8+ T cells to lyse M. tuberculosis-infected target cells required cell-cell contact between NK cells and infected monocytes and depended on interactions between the CD40 ligand on NK cells and CD40 on infected monocytes. NK cells link the innate and the adaptive immune responses by optimizing the capacity of CD8+ T cells to produce IFN-γ and to lyse infected cells, functions that are critical for protective immunity against M. tuberculosis and other intracellular pathogens.

Original languageEnglish
Pages (from-to)130-137
Number of pages8
JournalJournal of Immunology
Volume172
Issue number1
DOIs
StatePublished - 1 Jan 2004

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Natural Killer Cells
Mycobacterium tuberculosis
T-Lymphocytes
Interleukin-15
Interleukin-18
Monocytes
Monokines
CD40 Ligand
Tuberculin
Adaptive Immunity
Phagocytes
Innate Immunity
Immunity

Cite this

Vankayalapati, R., Klucar, P., Wizel, B., Weis, S., Samten, B., Safi, H., ... Barnes, P. F. (2004). NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen. Journal of Immunology, 172(1), 130-137. https://doi.org/10.4049/jimmunol.172.1.130
Vankayalapati, Ramakrishna ; Klucar, Peter ; Wizel, Benjamin ; Weis, Stephen ; Samten, Buka ; Safi, Hassan ; Shams, Homayoun ; Barnes, Peter F. / NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen. In: Journal of Immunology. 2004 ; Vol. 172, No. 1. pp. 130-137.
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Vankayalapati, R, Klucar, P, Wizel, B, Weis, S, Samten, B, Safi, H, Shams, H & Barnes, PF 2004, 'NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen', Journal of Immunology, vol. 172, no. 1, pp. 130-137. https://doi.org/10.4049/jimmunol.172.1.130

NK Cells Regulate CD8+ T Cell Effector Function in Response to an Intracellular Pathogen. / Vankayalapati, Ramakrishna; Klucar, Peter; Wizel, Benjamin; Weis, Stephen; Samten, Buka; Safi, Hassan; Shams, Homayoun; Barnes, Peter F.

In: Journal of Immunology, Vol. 172, No. 1, 01.01.2004, p. 130-137.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Vankayalapati, Ramakrishna

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AU - Wizel, Benjamin

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AU - Samten, Buka

AU - Safi, Hassan

AU - Shams, Homayoun

AU - Barnes, Peter F.

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