Submitted May 17, 2006
Accepted September 5, 2006
Distinct memory CD4+ T cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers
Kevin N. Heller, Jenica Upshaw, Beza Seyoum, Henry Zebroski, and Christian Munz*
Laboratory of Viral Immunobiology, Rockefeller University, New York, NY, USA
Proteomics Resource Center, Rockefeller University, New York, NY, USA
* Corresponding author; email: munzc{at}rockvax.rockefeller.edu.
CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1 specific effector CD4+ T cells are primarily TH1 polarized. Here we show that most healthy EBV carriers have such IFN
secreting EBNA1 specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory cell subsets. Despite continuous antigen presence due to persistent EBV infection half of the proliferating EBNA1 specific CD4+ T cells belonged to the central memory compartment (TCM). The remaining EBNA1 specific CD4+ T cells displayed an effector memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1 specific TCM CD4+ T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1 polarized effector cells.
