Differential Kinetics and Specificity of EBV-Specific CD4+ and CD8+ T Cells During Primary Infection

• Published in: The Journal of immunology (1950) Vol. 170; no. 5; pp. 2590 - 2598
• Main Authors: Precopio, Melissa L, Sullivan, John L, Willard, Courtney, Somasundaran, Mohan, Luzuriaga, Katherine
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.03.2003
• Subjects: Acute Disease; Adult; Amino Acid Sequence; Antigen Presentation; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell Division - immunology; Epitopes, T-Lymphocyte - immunology; Epstein-Barr Virus Nuclear Antigens - immunology; Herpesvirus 4, Human - immunology; Humans; Infectious Mononucleosis - blood; Infectious Mononucleosis - immunology; Infectious Mononucleosis - virology; Lymphocyte Count; Molecular Sequence Data; Nuclear Proteins - immunology; Phosphoproteins - immunology; Trans-Activators - immunology; Transcription Factors - immunology; Viral Load; Viral Proteins
• DOI: 10.4049/jimmunol.170.5.2590
• ISSN: 0022-1767

The generation and maintenance of virus-specific CD4(+) T cells in humans are not well understood. We used short in vitro stimulation assays followed by intracellular cytokine staining to characterize the timing, magnitude, and Ag specificity of CD4(+) T cells over the course of primary EBV infection. Lytic and latent protein-specific CD4(+) T cells were readily detected at presentation with acute infectious mononucleosis and declined rapidly thereafter. Responses to BZLF-1, BMLF-1, and Epstein-Barr nuclear Ag-3A were more commonly detected than responses to Epstein-Barr nuclear Ag-1. Concurrent analyses of BZLF-1-specific CD4(+) and CD8(+) T cells revealed differences in the expansion, specificity, and stability of CD4(+) and CD8(+) T cell-mediated responses over time. Peripheral blood EBV load directly correlated with the frequency of EBV-specific CD4(+) T cell responses at presentation and over time, suggesting that EBV-specific CD4(+) T cell responses are Ag-driven.