Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance.
Patients with infectious mononucleosis (IM) undergoing primary EBV infection show large expansions of EBV-specific CD8+ T cells in the blood. While latent infection of the B cell pool is quickly controlled, virus shedding from lytically infected cells in the oropharynx remains high for several months. We therefore studied how responses localize to the tonsil, a major target site for EBV, during primary infection and persistence. In acute IM, EBV-specific effectors were poorly represented among CD8+ T cells in tonsil compared with blood, coincident with absence of the CCR7 lymphoid homing marker on these highly activated cells. In patients who had recently recovered from IM, latent epitope reactivities were quicker than lytic reactivities both to acquire CCR7 and to accumulate in the tonsil, with some of these cells now expressing the CD103 integrin, which mediates retention at mucosal sites. By contrast, in long-term virus carriers in whom both lytic and latent infections had been controlled, there was 2- to 5-fold enrichment of lytic epitope reactivities and 10- to 20-fold enrichment of latent epitope reactivities in tonsil compared with blood; up to 20% of tonsillar CD8+ T cells were EBV specific, and many now expressed CD103. We suggest that efficient control of EBV infection requires appropriate CD8+ T cell homing to oropharyngeal sites.
Hislop
Andrew D
AD
Institute for Cancer Studies and Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom.
Kuo
Michael
M
Drake-Lee
Adrian B
AB
Akbar
Arne N
AN
Bergler
Wolfgang
W
Hammerschmitt
Nicolas
N
Khan
Naeem
N
Palendira
Umaimainthan
U
Leese
Alison M
AM
Timms
Judith M
JM
Bell
Andrew I
AI
Buckley
Christopher D
CD
Rickinson
Alan B
AB
D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002353:Carrier State; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000821:virology; D014066:Palatine Tonsil / Q000276:immunology* / Q000821:virology*; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D019562:Viral Load
D015703:Antigens, CD; C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine