Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL<sup>+</sup>T and B Cells during Murine<i>Schistosoma mansoni</i>Infection

Lundy, Steven K.; Lerman, Stephen J.; Boros, Dov L.

doi:10.1128/iai.69.1.271-280.2001

Cited by 97 publications

(95 citation statements)

References 36 publications

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“…Lundy and others also demonstrated that in vitro culture with SEA induced Fas L expression on splenic but not granuloma CD4 ϩ , CD8 ϩ and CD19 ϩ cells. 7 Failure of granuloma lymphocytes to upregulate FasL in vitro is consistent with our results, which showed that granuloma lymphocytes expressed two-fold higher levels of FasL in vivo compared with splenic lymphocytes ( Figure 6). Given this high level of FasL expression in vivo, it is not surprising that granuloma lymphocytes are less responsive to additional in vitro stimulation.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Rumbley¹,

Sugaya²,

Zekavat³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Infection with the helminth parasite Schistosoma mansoni is associated with a pathogenic granulomatous response to parasite eggs. Multiple cell types constitute the granuloma with eosinophils achieving numerical dominance. We hypothesize that eosinophil dominance is achieved by selective apoptosis in lymphocytes. We report here that lymphocytes from both the spleens and granulomas of S. mansoni-infected mice undergo apoptosis. We also show that granuloma lymphocytes are more susceptible to Fas-FasL-mediated apoptosis than spleen lymphocytes and this apoptosis may be related to antigen concentration. Conversely, eosinophils from the granuloma and spleens of S. mansoni-infected mice are resistant to apoptosis in vivo and are protected in vitro from Fas-FasL-mediated apoptosis by the absence of FasL expression in the presence of Fas expression. Finally, the apoptotic regulatory molecules Bcl-2, Bcl-xL, and Bax, do not appear to play a significant role in the regulation of eosinophil apoptosis in the schistosome granuloma.

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Section: Discussionsupporting

confidence: 81%

“…This selective destruction may result from antigen-driven, Fas-FasLdependent apoptosis. 7 Thus, ''granuloma-specific'' regulation may protect the host from systemic pathologic consequences such as fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Rumbley¹,

Sugaya²,

Zekavat³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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“…CXCL10 is a potent Th1-associated chemokine 68 whereas CXCL13 is the major chemoattractant for B cells, which can induce the apoptosis of CD4(ϩ) T cells during schistosomal granuloma responses. 69 In contrast, the immunoneutralization of CCL22, which had the most dramatic effect on all granulomatous parameters examined selectively increased IFN-␥. Thus, although CCL17 and CCL22 have demonstrable regulatory effects on the secondary granulomatous response to S. mansoni eggs, it is plausible that the mechanism through which this regulation is achieved differs markedly between the two CCR4 ligands.…”

Section: Discussionmentioning

confidence: 92%

Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Jakubzick

Wen

Matsukawa

et al. 2004

The American Journal of Pathology

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Controversy persists pertaining to the role of CCR4 ligands, namely CCL17 (or thymus and activation regulated chemokine; TARC) and CCL22 (or macrophagederived chemokine; MDC), in Th2-type cytokine-dominated responses in the lung. Accordingly, the present study addressed the relative role of each of these CC chemokines during an evolving pulmonary granulomatous response elicited by the intrapulmonary embolization of live Schistosoma mansoni eggs into S. mansoni-sensitized mice. CCL22 protein expression peaked at day 4, but CCL17 levels were not increased significantly at any time after egg challenge. CCR4 transcript and protein expression were highest at day 8 after egg embolization and CCR4 protein was prominently expressed in macrophages surrounding S. mansoni eggs. Systemic immunoneutralization of CCL22 from the time of egg injection into S. mansonisensitized mice for 8 days significantly decreased CCR4 protein expression, the eosinophil content, the overall size of the egg granuloma, and its hydroxyproline content. Whole lung levels of interferon-␥ were also significantly increased at day 8 in anti-CCL22-treated mice. The systemic immunoneutralization of CCL17 had a lesser effect on all of the granuloma parameters listed above, but this antibody treatment significantly decreased granuloma hydroxyproline content to a greater extent than the anti-CCL22 antibody treatment. In addition, the immunoneutralization of CCL17 significantly increased whole lung levels of interleukin (IL)-4, IL-5, IL-13, transforming growth factor-␤, IL-12, and tumor necrosis factor-␣ at day 8 after egg infusion. Thus, these studies demonstrate a major role for CCL22 and a lesser role for CCL17 during an evolving S. mansoni egg granuloma in the lung. Understanding the biology of chemotactic cytokines or chemokines and their receptors continues to challenge a number of researchers working in diverse fields such as inflammation, immune regulation, angiogenesis, virology, and lymphoid development.

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“…It is unclear how these findings can be reconciled with the studies implicating CD8+ cells in downregulation of granuloma size. Rumbley et al (1998Rumbley et al ( , 2001 hypothesize that selective apoptosis of sensitized lymphocytes within the granulomas contributes to immunoregulation (Rumbley et al 1998, Lundy et al 2001, Lundy & Boros 2002.…”

Section: The Role Of Cytokines In Granuloma Formation and Downregulatmentioning

confidence: 99%

Experimental models of Schistosoma mansoni infection

Cheever

Lenzi²,

Lenzi³

et al. 2002

Mem. Inst. Oswaldo Cruz

121

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Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL⁺T and B Cells during MurineSchistosoma mansoniInfection

Cited by 97 publications

References 36 publications

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Experimental models of Schistosoma mansoni infection

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Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL+T and B Cells during MurineSchistosoma mansoniInfection

Cited by 97 publications

References 36 publications

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Elimination of lymphocytes, but not eosinophils, by Fas-mediated apoptosis in murine schistosomiasis.

Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Experimental models of Schistosoma mansoni infection

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Product

Resources

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Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL⁺T and B Cells during MurineSchistosoma mansoniInfection