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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.

One or more keywords matched the following items that are connected to Selin, Liisa
Item TypeName
Academic Article A fractal clonotype distribution in the CD8+ memory T cell repertoire could optimize potential for immune responses.
Academic Article Plasticity of T cell memory responses to viruses.
Academic Article Complex T cell memory repertoires participate in recall responses at extremes of antigenic load.
Academic Article Anti-IFN-? and peptide-tolerization therapies inhibit acute lung injury induced by cross-reactive influenza A-specific memory T cells.
Academic Article Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis.
Academic Article Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
Academic Article CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections.
Academic Article Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes.
Concept Influenza, Human
Concept Influenza A virus
Academic Article PC61 (anti-CD25) treatment inhibits influenza A virus-expanded regulatory T cells and severe lung pathology during a subsequent heterologous lymphocytic choriomeningitis virus infection.
Academic Article Narrowing of human influenza A virus-specific T cell receptor a and ? repertoires with increasing age.
Academic Article Unique influenza A?cross-reactive memory CD8 T-cell receptor repertoire has a potential to protect against EBV seroconversion.
Academic Article Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires.
Academic Article Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old.
Search Criteria
  • Influenza Human