Protective role of γ/δ T cells and α/β T cells in tuberculosis

Ladel, Christoph; Blum, Carmen; Dreher, Anja; Reifenberg, Kurt; Kaufmann, Stefan H. E.

doi:10.1002/eji.1830251025

Cited by 215 publications

(141 citation statements)

References 20 publications

(12 reference statements)

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“…This cytokine is critical for host defenses, especially protection from intracellular pathogens and for tumor immunity (1,25), and its secretion by ␥␦ T cells is apparently critical for its function. For example, ␥␦ T cells play an important role in early protection from experimental Mycobacterium tuberculosis infection through IFN-␥ secretion (52,53). These T cells also contribute to the regulation of NK cell-mediated innate resistance against another intracellular pathogen, Listeria monocytogenes (54).…”

Section: Discussionmentioning

confidence: 99%

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

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γδ T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine γδ T cells acquire the capacity to differentially produce such cytokines. Splenic γδ T cells could be polarized into IFN-γ- or IL-4-secreting cells in vitro; however, in contrast to CD4+ αβ T cells, γδ T cells predominantly produced IFN-γ, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-γ-producing cells expressed the IL-12 receptor β2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed γδ T cells also expressed this receptor, even in the absence of IFN-γ and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed γδ T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-γ by γδ T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-γ by γδ T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.

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Section: Discussionmentioning

confidence: 99%

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

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“…The contribution of ␥/␦ T cells in various gene knockout or antibody depletion mouse models to virulent mycobacterial infection appears to depend on the route, dose, and challenge organism [19,20,33]. These parameters, especially dose (e.g., high or low), may or may not affect bacterial numbers in various tissues in addition to survival due to the apparent regulatory effects of ␥/␦ T lymphocytes on inflammation [20].…”

Section: Discussionmentioning

confidence: 99%

“…␥/␦ T cell subpopulations can express cytokines such as TNF-␣ and IFN-␥ in exclusive patterns and potentially provide helper activity to B cells through their expression of CD40L [17,18]. It is important to note that studies in TCR ␦ chain-deficient mice suggest that this cell population contributes to granuloma architecture and thus containment of bacterial dissemination [19,20].…”

Section: Introductionmentioning

confidence: 99%

Role of CD8+ and WC-1+ γ/δ T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse

Smith

Kreeger

Alvarez

et al. 1999

Journal of Leukocyte Biology

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The role of various effector T cell populations in the bovine immune response toMycobacterium bovis infection is poorly understood. This is largely due to the difficulties associated with performing in vivo challenge studies in the natural host species. In this report, we utilized a fetal bovine-severe combined immunodeficient (SCID-bo) xenochimeric mouse model to study the protective role of two putative effector cell types, CD8 ؉ T cells and a subpopulation of ␥/␦ T cells that express WC-1, a member of the cysteine-rich scavenger receptor superfamily (CRSR). We demonstrate that CD8 ؉ T cells play a key role in protection and contribute substantially to bovine IFN-␥ mRNA levels at 30 days post-infection. The role of WC-1 bearing cells to protection was less definitive but our results suggest that this population may play a pivotal role early in infection. Granuloma architecture was altered in anti-WC-1 (ILA29) but not anti-CD8 (ILA51) -treated animals, suggesting that this population may be involved in recruitment of various cell types to sites of infection. J. Leukoc. Biol. 65: 28-34; 1999.

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“…Notably, in TCRˇ-/-mice, densely focused granulomas contain abundant numbers of PMN [24]. This has been attributed to the general regulatory role of +ˇ+ T cells during mucosal immune responses [26] as well as the interplay with PMN during anti-tuberculous granuloma formation [24,27]. Here we analyzed the impact of PMN during the initial phase of an aerosol infection with M. tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

et al. 2003

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Among the first cells to invade a site of infection, polymorphonuclear neutrophils (PMN) play an important role in the control of numerous infections. While PMN are considered critical for control of acute infections, their role in chronic infections remains less well understood. Here we report that PMN are essential for accurate early granuloma formation during chronic M. tuberculosis infection without influencing mycobacterial growth restriction. The PMNmediated regulation of granuloma formation depended on chemokines signaling through CXCR3, in particular MIG, as indicated by immune histochemical analysis of lung sections from C57BL/6 wild-type and CXCR3 -/-mutant mice and supported by microarray transcriptome analysis. Hence, PMN play a central role in regulating the focal granulomatous response in the lung, and this early granuloma formation can be segregated from long-term protection against pulmonary M. tuberculosis infection.

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Protective role of γ/δ T cells and α/β T cells in tuberculosis

Cited by 215 publications

References 20 publications

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Role of CD8+ and WC-1+ γ/δ T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

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