Chapter 9 : Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections

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Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, Page 1 of 2

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The discovery of γ δ T cells originally occurred as an unexpected result of attempts to identify and clone the T-cell receptor (TCR). This chapter presents evidence that γ δ T cells are required in order to prevent the development of chronic disease, which in turn may be a contributing factor in determining whether a microbial pathogen is eradicated or becomes persistent. At first consideration, the numerous accounts of large numbers of γ δ T cells within the inflammatory lesions associated with autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis and its mouse model, experimental autoimmune encephalitis, would appear to indicate a pathogenic rather than immunoregulatory role for γ δ T cells. However, rather than being an indication of involvement in the pathogenesis of these disorders, it can be said that the presence of γ δ T cells is an attempt to downregulate the extent of inflammation associated with these diseases. It has been suggested, however, that γ δ T cells promote the influx of macrophages into the site of infection, resulting in the generation of granulomas, which are essential for bacterial clearance. This hypothesis is based on the finding that the production of macrophage-specific chemokines, such as macrophage inflammatory protein-1α (MlP-1α), MIP-1β, MIP-2, and methyl-accepting chemotaxis protein 1, is reduced in TCR-δ mice following infection. In other cases, however, the bacteria can be reactivated and cause clinical disease.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9

Key Concept Ranking

gamma delta T Cell
Major Histocompatibility Complex
Tumor Necrosis Factor alpha
Infection and Immunity
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(A) Proposed functions for γδ T cells following infection with intracellular bacteria. (B) Kinetics of the growth of and the expansion of γδ T cells in the spleens of mice following infection. Mice were infected with 2 × 10 CFU of ,and the spleens were harvested on the indicated days. Bacterial numbers were determined by plating dilutions of organ homogenates on Luria-Bertani agar plates. γδ T-cell numbers were determined by flow cytometry. The expansion of Vδ6 and Vδ4 γδ T cells, which are the predominant populations that respond to infection with ,occurs when the bacterial numbers are in decline ( ). MΦmacrophage.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
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Image of FIGURE 2

TCR-δ-/- mice develop necrotic liver abscesses following infection with . Wild-type (A) and TCR-δ-/- (B) mice were infected for 6 days with 2 × 104 CFU of , and liver sections were stained with hematoxylin and eosin. Magnification, × 352.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
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Image of FIGURE 3

Proposed modulatory function of γδ T cells during the inflammatory response to infection with intracellular bacteria. According to this model, γδ T cells respond to stimulatory ligands, such as Hsp60, expressed by activated macrophages at the conclusion of an immune response to infection. Activated γδ T cells then acquire cytotoxic activity to kill the macrophage. In the absence of γδ T cells, activated macrophages accumulate in the animal, resulting in tissue necrosis as a result of overproduction of inflammatory mediators.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
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Contrasting features and properties of y8 T cells and other lymphocyte lineages

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9

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