Differential kinetics and specificity of EBV-specific CD4+ and CD8+ T cells during primary infection.
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.
Precopio
Melissa L
ML
Graduate Program in Immunology/Virology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Sullivan
John L
JL
Willard
Courtney
C
Somasundaran
Mohan
M
Luzuriaga
Katherine
K
D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002455:Cell Division / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000097:blood / Q000276:immunology* / Q000821:virology*; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins
C105528:BLZF1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; D010750:Phosphoproteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins