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Search Results to Liisa K Selin MD, PhD

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Academic Background

Dr. Liisa K. Selin received her B.Sc. degree (Biology and Psychology) in 1974 and M.D. degree in 1979, both from Dalhousie University, Halifax, Nova Scotia. She is Board Certified in Internal Medicine (1984, in Canada ), with fellowship training in infectious diseases. She also completed her PhD training in microbiology and immunology at the University of Manitoba, Winnipeg, Manitoba (Canada) in 1993 followed by 2 years of postdoctoral training at the University of Massachusetts Medical School, Worcester, MA. She joined the faculty in the Dept. of Pathology at the University of Massachusetts Medical School as an Instructor in 1994 and was promoted to her present position as Associate Professor in 2001. Dr. Selin has studied the role of T cells in response to viral infections; specifically, initially identifying and focusing on the phenomenon of heterologous immunity, whereby memory T cell responses to pathogens can influence the outcome to subsequent infection with unrelated pathogens. The effects of heterologous immunity are now known, at least in part, to be mediated by cross-reactive T cell responses and mediate both protective effects, immune enhancement and can induce immunopathology. In the past decade she has published and spoken on numerous aspects of the heterologous immunity and CD8 T cell cross-reactivity.

Liisa_Selin

Mechanisms of viral immunology: heterologous immunity and CD8 T cell crossreactivity during viral infections.

A comprehensive understanding of the mechanisms associated with the generation and modulation of immunological T cell memory will lead to a better understanding of how the immune system controls viral infections but also causes immune-mediated pathology. Our studies with viruses in murine systems have focused on virus-specific memory T cell populations, which demonstrate plasticity in antigen recognition and in their ability to accommodate new memory T cell populations. Memory T cells laid down as a consequence of one infection can influence protective immunity and immunopathology associated with a second unrelated virus. We have referred to this phenomenon as T cell-dependent heterologous immunity and immunopathology. The focus of our work is to develop a better understanding of the mechanisms associated with the induction of heterologous immunity, specifically the role cross-reactive memory T cell responses and cytokines play in decreasing or augmenting viral replication and altering immunopathology. We have identified a matrix of cross-reactive epitopes between viruses, and developed both systemic and respiratory infection model systems. We use several virus systems, but focus on lymphocytic chorimeningitis (LCMV) and Pichinde (PV) viruses, distantly related arenaviruses whose T cell responses are well defined, and on the poxvirus vaccinia (VV), which is used as a vaccine for smallpox and as a recombinant vaccine and vector for many antigens.

Our studies in human viral infections on heterologous immunity and cross-reactive T cell responses during Epstein Barr virus (EBV) infection only begin to scratch the surface of the prevalence and potential impact of cross-reactive T cell responses on both vaccine development and immunopathology. There is very little understanding of the structural and functional interaction of one TCR with two different ligands. We have identified directly ex vivo and in bulk T cell cultures HLA-A2-restricted cross-reactive CD8 T cell responses that recognize both EBV BMLF-1 and influenza A M1 HLA-A2 restricted epitopes. These cross-reactive T cells were found to participate in acute infectious mononucleosis (IM). Five of 8 young adult HLA-A2+ patients experiencing IM had an increased number of influenza virus (FLU)-M158-66 specific CD8+ T cells in their peripheral blood as compared to healthy donors. Two of 5 IM patients with augmented FLU-M1 responses had high levels of tetramer-defined cross-reactive cells as measured directly ex vivo in their peripheral blood. EBV likely activates multiple populations of cross-reactive memory cells involved in the development of IM, and we have been able to provide evidence that those specific to FLU-M1 can contribute to this phenomenon. In order to better understand how cross-reactive CD8 T cells may be modulating disease outcome by enhancing viral clearance or inducing immunopathology, such as that seen in IM, we continue to characterize the cross-reactive TCR, both functionally and structurally, and examine how cross-reactivity influences the evolution of antigen-specific TCR repertoire development and disease outcome in both mice and humans during viral infections.

Rotation Projects

Rotation Projects for graduate students:

  1. Examining the role of cross-reactive CD8 memory T cells in mediating the EBV-induced infectious mononucleosis syndrome in humans.
  2. Examining the role of cross-reactive CD8 memory T cells and cytokines in murine models of viral infection. Examining the mechanisms used by these memory T cells to unrelated infections to modulate disease outcome either for the bad or the good.

One or more keywords matched the following items that are connected to Selin, Liisa

Item TypeName
Academic Article Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections.
Academic Article Role of apoptosis in the regulation of virus-induced T cell responses, immune suppression, and memory.
Academic Article Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection.
Academic Article Protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory T cell populations.
Academic Article Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: relative stability of CD4 memory under conditions of CD8 memory T cell loss.
Academic Article T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens.
Academic Article Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation.
Academic Article Heterologous immunity and the CD8 T cell network.
Academic Article A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses.
Academic Article Virus-specific CD8 T cells in peripheral tissues are more resistant to apoptosis than those in lymphoid organs.
Academic Article Plasticity of T cell memory responses to viruses.
Academic Article Immunological memory to viral infections.
Academic Article CD8 T cell responses to viral infections in sequence.
Academic Article Embedding T cells in the matrix.
Academic Article CD8 memory T cells: cross-reactivity and heterologous immunity.
Academic Article Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses.
Academic Article IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections.
Academic Article Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity.
Academic Article Consequences of cross-reactive and bystander CTL responses during viral infections.
Academic Article Complex T cell memory repertoires participate in recall responses at extremes of antigenic load.
Academic Article Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung.
Academic Article Resistance to vaccinia virus is less dependent on TNF under conditions of heterologous immunity.
Academic Article Heterologous immunity between viruses.
Academic Article No one is naive: the significance of heterologous T-cell immunity.
Academic Article Anti-IFN-? and peptide-tolerization therapies inhibit acute lung injury induced by cross-reactive influenza A-specific memory T cells.
Academic Article Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein.
Academic Article Private specificities of CD8 T cell responses control patterns of heterologous immunity.
Academic Article Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis.
Academic Article Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity.
Academic Article The privacy of T cell memory to viruses.
Academic Article Protection against vaccinia virus challenge by CD8 memory T cells resolved by molecular mimicry.
Academic Article Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
Academic Article A discrete computer model of the immune system reveals competitive interactions between the humoral and cellular branch and between cross-reacting memory and naïve responses.
Academic Article Attrition of memory CD8 T cells.
Academic Article Epitope specificity and relative clonal abundance do not affect CD8 differentiation patterns during lymphocytic choriomeningitis virus infection.
Academic Article CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections.
Academic Article Systematic simulation of cross-reactivity predicts ambiguity in Tk memory: it may save lives of the infected, but limits specificities vital for further responses.
Academic Article Computer simulations of heterologous immunity: highlights of an interdisciplinary cooperation.
Academic Article Specificity and editing by apoptosis of virus-induced cytotoxic T lymphocytes.
Academic Article Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses.
Concept Immunologic Memory
Academic Article Vaccination and heterologous immunity: educating the immune system.
Academic Article Evaluation of non-reciprocal heterologous immunity between unrelated viruses.
Academic Article Increased Immune Response Variability during Simultaneous Viral Coinfection Leads to Unpredictability in CD8 T Cell Immunity and Pathogenesis.
Academic Article Unique Influenza A crossreactive memory CD8 TCR repertoire has a potential to protect against Epstein Barr virus seroconversion.
Academic Article Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory.

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