GSBS Student Publications

Title

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

Student Author(s)

Shalyn Clute; Levi B. Watkin

GSBS Program

Immunology & Virology Program

UMMS Affiliation

Department of Pathology; Department of Pediatrics; Program in Molecular Medicine

Date

12-1-2005

Document Type

Article

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

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences

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 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.

Rights and Permissions

Citation: J Clin Invest. 2005 Dec;115(12):3602-12. Epub 2005 Nov 23. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

The Journal of clinical investigation

PubMed ID

16308574