Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis
Department of Pathology; Department of Pediatrics; Program in Molecular Medicine
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
The marked proliferation of activated CD8+ T cells is pathognomonic of EBV-associated infectious mononucleosis (IM), common in young adults. Since the diversity and size of the memory CD8+ T cell population increase with age, we questioned whether IM was mediated by the reactivation of memory CD8+ T cells specific to previously encountered pathogens but cross-reactive with EBV. Of 8 HLA-A2+ IM patients, 5 had activated T cells specific to another common virus, as evidenced by a significantly higher number of peripheral blood influenza A virus M1(58-66)-specific T cells compared with healthy immune donors. Two patients with an augmented M1 response had tetramer-defined cross-reactive cells recognizing influenza M1 and EBV-BMLF1(280-288), which accounted for up to one-third of their BMLF1-specific population and likely contributed to a skewed M1-specific T cell receptor repertoire. These epitopes, with only 33% sequence similarity, mediated differential effects on the function of the cross-reactive T cells, which may contribute to alterations in disease outcome. EBV could potentially encode an extensive pool of T cell epitopes that activate other cross-reactive memory T cells. Our results support the concept that cross-reactive memory CD8+ T cells activated by EBV contribute to the characteristic lymphoproliferation of IM.
DOI of Published Version
J Clin Invest. 2005 Dec;115(12):3602-12. Epub 2005 Nov 23. Link to article on publisher's site
The Journal of clinical investigation
Clute SC, Watkin LB, Cornberg M, Naumov YN, Sullivan JL, Luzuriaga K, Welsh RM, Selin LK. (2005). Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. GSBS Student Publications. https://doi.org/10.1172/JCI25078. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/241