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Antigen-specific memory T cell distribution in non-lymphoid tissue

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dc.contributor.advisor Paul T. Matsudaira and Jianzhu Chen. en_US
dc.contributor.author Olurinde, Mobolaji O en_US
dc.contributor.other Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.date.accessioned 2008-03-27T18:27:16Z
dc.date.available 2008-03-27T18:27:16Z
dc.date.copyright 2007 en_US
dc.date.issued 2007 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/40951
dc.description Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. en_US
dc.description Includes bibliographical references (leaves 28-34). en_US
dc.description.abstract CD8+ T cells are the main adaptive immune system cell type responding to intracellular pathogens, particularly viruses, and tumor antigens. In the case of influenza, activated T cells migrate from the mediastinal (draining) lymph nodes to the lung where they perform their cytolytic function. After pathogen clearance, memory CD8+ T cells are generated, giving rise to long-term protection from reinfection. However, these cells are no longer detectable in the lung parenchyma six months post-infection, and cell-mediated immunity, and protection is lost. Knock-out studies in mice show that interleukin 15 (IL-15) is essential for memory CD8+ T cell proliferation. Fibroblasts, macrophages, dendritic cells and epithelial cells express IL-15 and its receptor isoform [alpha] (IL-15R[alpha]). Histological studies suggest that memory CD8+ T cells preferentially reside in peribronchiolar and perivascular areas, the stroma, of the lung. We hypothesize that memory CD8+ T cells preferentially reside in regions where molecules necessary for their maintenance, for example, IL-15/R secreting cells, are located. In this study, we have shown that antigen-specific 2C GFP effector memory CD8+ T cells are generated in B6 recipient mice 30-32 days after influenza virus infection, preferentially reside in peribronchiolar areas. Both 2C and 2C GFP recipient mice have severe vasculitis and widely distributed inflammatory infiltrates 7 days post-infection. Lower lung lobes appear to be more affected than upper lobes at this time point. On day 30, most of the airways have been cleared and restored. Although lymphoid-appearing nodules were detected in the lungs 31 dpi, no clusters of B cells and T cells suggesting induced BALT were identified by immunofluorescence. en_US
dc.description.abstract (cont.) Interestingly, antigen-specific GFP cells preferentially remained in the lung tissue and were almost undetectable in spleens, lymph nodes, and livers. This preference was not observed in 2C (non-GFP) recipient mice. Immunofluorescence studies showed no colocalization between 2C GFP T cells and dendritic cells that might suggest stable dendritic cell interactions contribute to antigen-specific cells preferentially residing in the lung stroma. Further studies are necessary to determine what other cell types might contribute to this phenomenon. These results provide some insight into how structural elements in non-lymphoid tissue influence cell-mediated immunity. en_US
dc.description.statementofresponsibility by Mobolaji O. Olurinde. en_US
dc.format.extent 36 leaves en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/7582 en_US
dc.subject Biological Engineering Division. en_US
dc.title Antigen-specific memory T cell distribution in non-lymphoid tissue en_US
dc.type Thesis en_US
dc.description.degree S.M. en_US
dc.contributor.department Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.identifier.oclc 212628036 en_US


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