Exaggerated Proinflammatory and Th1 Responses in the Absence of γ/δ T Cells after Infection with<i>Listeria monocytogenes</i>

Skeen, Marianne J.; Rix, Emily Parker; Freeman, Molly M.; Ziegler, H.

doi:10.1128/iai.69.12.7213-7223.2001

Cited by 35 publications

(36 citation statements)

References 53 publications

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“…Although TCR␥␦ ϩ T cells have been proposed to play a role in early innate immune responses, they could also down-modulate the immune response as infection is resolved or possibly as a result of an infection being uncontrolled. In support of this hypothesis, it has been found that in the absence of TCR␥␦ ϩ T cells, abnormally large granulomatous responses persist after infection with L. monocytogenes or M. tuberculosis (83,93), and mice depleted of TCR␥␦ ϩ T cells have an exaggerated proinflammatory response to L. monocytogenes infection (93). Other evidence indicates that TCR␥␦ ϩ T cells can inhibit various immune functions (65).…”

Section: Figure 6 Tcr␥␦mentioning

confidence: 61%

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

Klimpel

Matthias

Vinetz

2003

The Journal of Immunology

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Innate and adaptive immune responses induced by leptospirosis have not been well characterized. In this study we show that in vitro exposure of naive human PBMC to Leptospira interrogans results in cell proliferation and the production of IFN-γ, IL-12, and TNF-α. Cell proliferation was highest when using high numbers of Leptospira. Optimal cell proliferation occurred at 6–8 days, and the majority of cells contained in these cultures were γ/δ T cells. These cultures showed a 10- to 50-fold expansion of γ/δ T cells compared with the initial cellular input. Additionally, these cultures contained elevated numbers of NK cells. In contrast, exposure of PBMC to low numbers of Leptospira failed to induce γδ T cell or NK cell expansion, but induced significant αβ T cell expansion. Vγ9/Vδ2 were expressed on all γ/δ T cells expanded by exposure of PBMC to Leptospira. Leptospira stimulation of purified TCRγδ+ T cells, obtained from 8-day cultures of Leptorspira-stimulated PBMC, induced high levels of IFN-γ production, but no cell proliferation, suggesting that such stimulation of γδ T cells did not depend on specialized accessory cells or Ag processing. Finally, in patients with acute leptospirosis, there was a significant (4- to 5-fold) increase in the number of peripheral blood TCRγδ+ T cells. These results indicate that Leptospira can activate γδ T cells and αβ T cells and will guide further investigations into the roles of these T cell populations in host defense and/or the pathology of leptospirosis.

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Section: Figure 6 Tcr␥␦mentioning

confidence: 61%

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

Klimpel

Matthias

Vinetz

2003

The Journal of Immunology

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“…However, the histology was different in aerosol infection in mice lacking ␥␦ cells, in that a substantial pyogenic form of the granulomatous response was seen compared with the lymphocytic response detected in wildtype mice (41). This indicates that ␥␦ cells play an important protective role at high levels of mycobacteria inocula, while at lower levels of inocula they play a regulatory (anti-inflammatory) role by limiting the influx of inflammatory cells and consequently tissue damage (42).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Lung γδ T Cells Following Intranasal Infection withMycobacterium bovisBacillus Calmette-Guérin

Dieli

Iványi

Marsh

et al. 2003

The Journal of Immunology

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The lungs are considered to have an impaired capacity to contain infection by pathogenic mycobacteria, even in the presence of effective systemic immunity. In an attempt to understand the underlying cellular mechanisms, we characterized the γδ T cell population following intranasal infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). The peak of γδ T cell expansion at 7 days postinfection preceded the 30 day peak of αβ T cell expansion and bacterial count. The expanded population of γδ T cells in the lungs of BCG-infected mice represents an expansion of the resident Vγ2 T cell subset as well as an influx of Vγ1 and of four different Vδ gene-bearing T cell subsets. The γδ T cells in the lungs of BCG-infected mice secreted IFN-γ following in vitro stimulation with ionomycin and PMA and were cytotoxic against BCG-infected peritoneal macrophages as well as against the uninfected J774 macrophage cell line. The cytotoxicity was selectively blocked by anti-γδ TCR mAb and strontium ions, suggesting a granule-exocytosis killing pathway. Depletion of γδ T cells by injection of specific mAb had no effect on the subsequent developing CD4 T cell response in the lungs of BCG-infected mice, but significantly reduced cytotoxic activity and IFN-γ production by lung CD8 T cells. Thus, γδ T cells in the lungs might help to control mycobacterial infection in the period between innate and classical adaptive immunity and may also play an important regulatory role in the subsequent onset of αβ T lymphocytes.

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“…Previously, two reports used γδ T cell-deficient mice to determine their role during bacterial infections. Skeen et al [6] infected mice i.p. with the gram-positive bacterium Listeria monocytogenes, resulting in infection of the intestinal epithelium.…”

Section: Introductionmentioning

confidence: 99%

γδ T cells mitigate the organ injury and mortality of sepsis

Tschöp

Martignoni

Goetzman

et al. 2007

Journal of Leukocyte Biology

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Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. γδ T cells are found largely in epithelial-rich tissues, and previous studies of γδ T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of γδ T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in γδ T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in γδ T cell-deficient mice, yet antibiotic treatment did not change mortality. Additionally, we found that recruitment of neutrophils and myeloid suppressor cells to the site of infection was diminished in γδ T cell-deficient mice. Finally, we found that circulating levels of IFN-γ were increased, and systemic levels of IL-10 were decreased in γδ T cell-deficient mice after CLP compared with wild-type mice. γδ T celldeficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN-γ abrogated the increase in intestinal permeability in γδ T cell-deficient mice. The intestines taken from γδ T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that γδ T cells modulate the response to sepsis and may be a potential therapeutic target.

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Exaggerated Proinflammatory and Th1 Responses in the Absence of γ/δ T Cells after Infection withListeria monocytogenes

Cited by 35 publications

References 53 publications

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

Characterization of Lung γδ T Cells Following Intranasal Infection withMycobacterium bovisBacillus Calmette-Guérin

γδ T cells mitigate the organ injury and mortality of sepsis

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