Roles of reactive nitrogen intermediates and transforming growth factor-β produced by immunosuppressive macrophages in the expression of suppressor activity against T cell proliferation induced by TCR stimulation

Shimizu, Toshiaki; Cai, Shanshan; Tomioka, Haruaki

doi:10.1016/j.cyto.2004.12.016

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Data are representative of two separate studies. ns, Not significant; *, P Յ 0.05. tissues, including IL-10, TGF-␤, PGE 2 , and NO [43,44]. So, it might not be unexpected that normal intestinal MØ may also suppress the immune reactivity of other cell types within the interstitial tissues.…”

Section: Discussionmentioning

confidence: 93%

Suppression of experimental colitis by intestinal mononuclear phagocytes

Qualls

Kaplan

Rooijen

et al. 2006

Journal of Leukocyte Biology

219

173

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The contribution of innate immunity to inflammatory bowel disease (IBD) remains an area of intense interest. Macrophages (MØ) and dendritic cells (DC) are considered important factors in regulating the onset of IBD. The goal of this study was to determine if intestinal mononuclear phagocytes (iMNP) serve a pathological or protective role in dextran sulfate sodium (DSS)-induced colitis in mice. Using a conditional MØ/DC depletion transgenic mouse line--MØ Fas-induced apoptosis--to systemically deplete iMNP, DSS colitis histopathology was shown to be more severe in MØ/DC-depleted compared with MØ/DC-intact mice. Similarly, localized iMNP depletion by clodronate-encapsulated liposomes into C57BL/6, BALB/c, and CB.17/SCID mice also increased DSS colitis severity, as indicated by increased histopathology, weight loss, rectal bleeding, decreased stool consistency, and colon length compared with MØ/DC-intact, DSS-treated mice. Histology revealed that iMNP depletion during DSS treatment led to increased neutrophilic inflammation, increased epithelial injury, and enhanced mucin depletion from Goblet cells. iMNP depletion did not further elevate DSS-induced expression of TNF-alpha and IFN-gamma mRNA but significantly increased expression of CXCL1 chemokine mRNA. Myeloperoxidase activity was increased in colons of MØ/DC-depleted, DSS-treated mice, compared with DSS alone, coincident with increased neutrophil infiltration in diseased colons. Neutrophil depletion combined with MØ/DC depletion prevented the increase in DSS colitis severity compared with MØ/DC depletion alone. This study demonstrates that iMNP can serve a protective role during development of acute colitis and that protection is associated with MØ/DC-mediated down-regulation of neutrophil infiltration.

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Section: Discussionmentioning

confidence: 93%

Suppression of experimental colitis by intestinal mononuclear phagocytes

Qualls

Kaplan

Rooijen

et al. 2006

Journal of Leukocyte Biology

219

173

View full text Add to dashboard Cite

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“…It is also possible that highly activated macrophages inhibit T-cell activation during mycobacterial infections (38,56). Alternatively, apoptosis of alveolar macrophages and monocytes has been described as a consequence of M. tuberculosis infection (7).…”

Section: Discussionmentioning

confidence: 99%

Impaired Expression of Perforin and Granulysin in CD8⁺T Cells at the Site of Infection in Human Chronic Pulmonary Tuberculosis

et al. 2007

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Protective immunity in tuberculosis is dependent on the coordinated release of cytolytic effector molecules from effector T cells and the subsequent granule-associated killing of infected target cells. In this study, we investigated the expression of cytolytic (perforin and granzyme A) and antimicrobial (granulysin) molecules at the single-cell level in cryopreserved lung tissue from patients with chronic, progressive tuberculosis disease. Quantification of protein-expressing cells was performed by in situ imaging, while mRNA levels in the infected tissue were analyzed by real-time PCR. Persistent inflammation, including excessive expression of inducible nitric oxide synthase in CD68؉ macrophages and significant infiltration of CD3؉ , CD8 ؉ and CD4 ؉ T cells, was evident in tuberculosis lesions in all patients. However, despite the accumulation of CD3 ؉ T cells, perforin-and granulysin-expressing CD3 ؉ T cells were detected at two-to threefold-lower ratios in the tuberculosis lesions than in distal lung parenchyma and uninfected control lungs, respectively. This was evident at both the protein and mRNA levels. Moreover, perforin-and granulysin-expressing CD8 ؉ T cells were scarce in individual granulomas within the tuberculosis lesions. In contrast, significant up-regulation of granzyme A-expressing CD3 ؉ T cells was evident in the lesions from all patients. Confocal microscopy revealed coexpression of perforin and granulysin, primarily in CD8 ؉ T cells; however, this expression was lower in the tuberculosis lesions. These findings suggest that symptomatic, chronic tuberculosis disease is associated with insufficient up-regulation of perforin and granulysin coexpression in CD8؉ T cells at the local site of infection.

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“…In a murine model, Mycobacterium infections generate immunosuppressive macrophages that cause strong suppression of both concanavalin A-induced and TCR signal-induced T cell proliferation. In both cases NOS inhibitor (L-NMMA) strongly attenuated the suppressor activity of Mycobacterium-induced macrophages (Shimizu et al, 2005). Another survival mechanism that involves NOS2 and NO production has been demostrated in Bacillus anthracis.…”

Section: Bacteriamentioning

confidence: 98%