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. 2000 Nov;101(3):325-32.
doi: 10.1046/j.1365-2567.2000.00122.x.

An alphabeta T-cell-independent immunoprotective response towards gut coccidia is supported by gammadelta cells

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An alphabeta T-cell-independent immunoprotective response towards gut coccidia is supported by gammadelta cells

A L Smith et al. Immunology. 2000 Nov.

Abstract

Although gammadelta cells are commonly hypothesized to provide a 'first line of defence', gammadelta-cell-deficient mice are generally only marginally more susceptible to pathogens. Because gammadelta cells are enriched within epithelia, it is important to resolve whether immunoprotective capacity towards epithelial-tropic pathogens is absent from the gammadelta-cell compartment, or whether such activity is present but simply redundant with that of alphabeta T cells. In this work, following infection of the intestinal epithelium of alphabeta T-cell-deficient mice with the coccidian parasite, Eimeria vermiformis, gammadelta cells were shown to support the rapid activation of other lymphoid cells and to confer a transferable antipathogen effect that could be eradicated by neutralization of interferon-gamma VSports手机版. However, unlike alphabeta T cells, these effects of gammadelta cells showed no evidence of functional immunological memory. These results are directly relevant to coccidiosis, an economically significant disease of livestock, and should have general relevance to infections involving alphabeta T-cell deficiencies, e. g. cryptosporidiosis in patients with acquired immune deficiency syndrome (AIDS). .

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Figures (V体育ios版)

Figure 1
Figure 1
Cellularity of mesenteric lymph nodes (MLNs) from T-cell receptor (TCR)-β–/– mice infected with Eimeria vermiformis. MLN cells were harvested, at the time-points indicated on the figure, from TCR-β–/– mice infected with 1000 sporulated oocysts. CD3+ cells were enumerated using flow cytometry with fluorescein isothiocyanate (FITC)-conjugated anti-CD3. Results are expressed as mean ± SE (n = 3 at each time-point). *Significant difference versus uninfected mice analysed in parallel (P < 0·05). p.i., postinfection.
Figure 2
Figure 2
Reconstitution of T-cell receptor (TCR)-(β × δ)–/– mice with mesenteric lymph node (MLN) cells from TCR-β–/– mice: phenotypic analysis. (a) TCR-β–/– MLN cells; donor cells. (b) Recipients, 3 months post-transfer. Representative flow cytometry plots from at least four individual mice are presented. Antibodies used were phycoerythrin (PE) -conjugated anti-γδ, -anti-CD3, -anti-B220, -anti-αIEL, and -anti-CD8-α, and fluorescein isothiocyanate-conjugated anti-CD3 and -anti-CD8β. iIEL, intestinal intraepithelial lymphocytes.
Figure 3
Figure 3
Adoptive transfer of T-cell receptor (TCR)-γδ T cells. Comparison of the efficacy of naive and responding (12 days postinfection) TCR-β–/– mesenteric lymph nodes (MLNs) as donor cells. (a) TCR-(β × δ)–/– mice received cells from naive TCR-β–/– mice (open bar); (b) and (c) TCR-(β × δ)–/– mice received cells from naive TCR-β–/– mice (open bars) or from infected mice (stippled bars), and were challenged once (panel b), rested, and then rechallenged (panel c). Results are expressed as mean ± SE from groups of four to 10 individually housed animals. Oocyst counts from adoptive-transfer recipients were comparable and statistically significantly different from counts from TCR-(β × δ)–/– mice that received phosphate-buffered saline (PBS) but no cells (P < 0·05). Fifty million TCR-β–/– MLN cells were adoptively transferred into TCR-(β × δ)–/– mice (both strains on a C57.BL/6 background). Primary infection was initiated with 100 sporulated oocysts 24–48 hr post-transfer, and secondary infection was initiated (with 100 oocysts) 4 weeks later.
Figure 4
Figure 4
Exacerbation of infection in T-cell receptor (TCR)-β–/– mice by anti-interferon-γ (IFN-γ) treatment. Results are expressed as mean ± SE from groups of five or six individually housed animals; the bar annotated ‘a’ was significantly different (P < 0·05) from the bars annotated with ‘b’. Mice were injected intravenously with 50 µg of rat anti-IFN-γ or rat immunoglobulin G (IgG) as indicated, and infected with sporulated oocysts 3 hr later.

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