ORCID Profile
0000-0001-8890-3228
Current Organisation
VIR Biotechnology (United States)
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Publisher: The American Association of Immunologists
Date: 15-03-2010
Abstract: The ersity of the pathogen-specific T cell repertoire is believed to be important in allowing recognition of different pathogen epitopes and their variants and thereby reducing the opportunities for mutation-driven pathogen escape. However, the extent to which the TCR repertoire can be manipulated by different vaccine strategies so as to obtain broad ersity and optimal protection is incompletely understood. We have investigated the influence of the infectious/inflammatory context on the TCR ersity of the CD8+ T cell response specific for the immunodominant epitope in C57BL/6 mice, derived from glycoprotein B of HSV-1. To that effect, we compared TCR V segment utilization, CDR3 length, and sequence ersity of the response to natural HSV-1 infection with those elicited by either Listeria monocytogenes or vaccinia virus expressing the immunodominant epitope in C57BL/6 mice. We demonstrate that although the type of infection in which the epitope was encountered can influence the magnitude of the CD8+ T cell responses, TCR β-chain repertoires did not significantly differ among the three infections. These results suggest that widely different live vaccine vectors may have little impact upon the ersity of the induced CTL response, which has important implications for the design of live CTL vaccine strategies against acute and chronic infections.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.EXGER.2014.03.020
Abstract: Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controversial. The attendees of the 4th International Workshop on "CMV & Immunosenescence", held in Parma, Italy, 25-27th March, 2013, presented and discussed data related to these open questions, which are reported in this commentary.
Publisher: The American Association of Immunologists
Date: 12-2012
Abstract: Persistent CMV infection has been associated with immune senescence. To address the causal impact of lifelong persistent viral infection on immune homeostasis and defense, we infected young mice systemically with HSV-1, murine CMV, or both viruses and studied their T cell homeostasis and function. Herpesvirus+ mice exhibited increased all-cause mortality compared with controls. Upon Listeria-OVA infection, 23-mo-old animals that had experienced lifelong herpesvirus infections showed impaired bacterial control and CD8 T cell function, along with distinct alterations in the T cell repertoire both before and after Listeria challenge, compared with age-matched, herpesvirus-free controls. Herpesvirus infection was associated with reduced naive CD8 T cell precursors above the loss attributable to aging. Moreover, the OVA-specific CD8 T cell repertoire recruited after Listeria challenge was entirely nonoverlapping between control and herpesvirus+ mice. To our knowledge, this study for the first time causally links lifelong herpesvirus infection to all-cause mortality in mice and to disturbances in the T cell repertoire, which themselves correspond to impaired immunity to a new infection in aging.
Publisher: Proceedings of the National Academy of Sciences
Date: 02-07-2018
Abstract: Epidemiological studies have shown a correlation between CMV infection and immune system aging, especially in elderly populations. It remains unclear whether CMV infection is a key driver of, or simply a factor associated with, aging of the immune system. We show that aging in the presence of lifelong CMV infection improves T cell immunity in old animals by broadening the immune response to a different pathogen. Animals that have aged with CMV are able to recruit novel T cells into these immune responses that are present in, but not utilized in, animals aging without CMV. These data squarely challenge the premise that CMV is solely detrimental to the aging of the adaptive immune system.
Location: United States of America
No related grants have been discovered for Megan Smithey.