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
Medical Subject Headings
Adolescent; Adult; CD8-Positive T-Lymphocytes; Cell Proliferation; Chemokine CCL4; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Epitopes; Flow Cytometry; Genes, MHC Class I; HLA-A2 Antigen; Herpesvirus 4, Human; Humans; Immunologic Memory; Infectious Mononucleosis; Influenza A virus; Interferon Type II; K562 Cells; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes; Macrophage Inflammatory Proteins; Orthomyxoviridae; Peptides; Receptors, Antigen, T-Cell; T-Lymphocytes; Time Factors
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.
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Citation: J Clin Invest. 2005 Dec;115(12):3602-12. Epub 2005 Nov 23. Link to article on publisher's site
DOI of Published Version
The Journal of clinical investigation
Clute, Shalyn Catherine; Watkin, Levi B.; Cornberg, Markus; Naumov, Yuri N.; Sullivan, John L.; Luzuriaga, Katherine; Welsh, Raymond M.; and Selin, Liisa K., "Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis" (2005). GSBS Student Publications. 241.