Submitted July 17, 2007
Accepted October 11, 2007
Repertoire and frequency of immune cells reactive to Epstein-Barr virus-derived autologous lymphoblastoid cell lines
Sumita Bhaduri-McIntosh*, Marisa J Rotenberg, Benjamin Gardner, Marie Robert, and George Miller
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, United States
Pediatric and Adolescent Medicine of Orange, Orange, CT, United States
Depts of Pediatrics, Molecular Biophysics & Biochemistry, and Epidemiology & Public Health, Yale University School of Medicine, New Haven, CT, United States
* Corresponding author; email: sumita.bhaduri-mcintosh{at}yale.edu.
Answers to questions regarding frequency and repertoire of immune cells, relative contributions made by different types of immune cells towards the total Epstein-Barr virus (EBV)-directed response, and the variation of such responses in healthy individuals have been elusive because of disparities in assays, antigen presenting cells, and antigenic sources used in previous experiments. In this study, we have addressed these questions using an assay that allowed direct comparison of responses generated by different types of cells of the immune system. This short-term (20hr) ex-vivo assay measured IFN
production by blood cells in response to autologous EBV-transformed lymphoblastoid cell lines (LCL). Our experiments defined the variation in responses among individuals and clearly distinguished ten healthy EBV-immune from ten healthy EBV-naive individuals. In EBV-immune individuals, 33% of responding cells were CD4+, 43.3% were CD8+, and 12.9% were -
T cells. LCL-reactive CD8+ T cells were only 1.7-fold more frequent than similarly-reactive CD4+ T cells. Responses by - T cells were six-fold higher in seropositive than in seronegative individuals. Our findings emphasize the importance of CD4+ and - T cell responses, have implications for immunotherapy, and for identifying defects in T cell populations that might predispose to development of EBV-associated lymphomas.
