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Cross-reactive influenza virus–specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus–associated infectious mononucleosis
Shalyn C. Clute, … , Raymond M. Welsh, Liisa K. Selin
Shalyn C. Clute, … , Raymond M. Welsh, Liisa K. Selin
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3602-3612. https://doi.org/10.1172/JCI25078.
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Research Article Immunology

Cross-reactive influenza virus–specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus–associated infectious mononucleosis

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Abstract

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 M158–66–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-BMLF1280–288, 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.

Authors

Shalyn C. Clute, Levi B. Watkin, Markus Cornberg, Yuri N. Naumov, John L. Sullivan, Katherine Luzuriaga, Raymond M. Welsh, Liisa K. Selin

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Figure 3

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Tetramer-defined subsets of cross-reactive T cells differ in their avidi...
Tetramer-defined subsets of cross-reactive T cells differ in their avidity for the 2 epitopes. A similar intracellular IFN-γ assay was performed on the same T cell line described in Figure 2, which had been grown in the presence of M1 and BMLF1 peptides for 4 weeks, using a titration of peptide concentrations. Filled triangles, tyrosinase; open circles, M1; and filled circles, BMLF1 stimulation. We assessed the IFN-γ production of gated, tetramer-defined subsets of the T cell line: (A) M1+ BMLF1+ and (B) M1– BMLF1+.
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