Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients
2015; eLife Sciences Publications Ltd; Volume: 4; Linguagem: Inglês
10.7554/elife.07916
ISSN2050-084X
AutoresCécile Alanio, Francesco Nicoli, Philippe Sultanik, Tobias Flecken, Brieuc P. Pérot, Darragh Duffy, Elisabetta Bianchi, Apiradee Lim, Emmanuel Clave, Marit M. van Buuren, Aurélie Schnuriger, Kerstin Johnsson, Jérémy Boussier, A. Garbarg‐Chenon, Laurence Bousquet, Estelle Mottez, Ton N. Schumacher, Antoine Toubert, Victor Appay, Farhad Heshmati, Robert Thimme, Stanislas Pol, Vincent Mallet, Matthew L. Albert,
Tópico(s)Cytomegalovirus and herpesvirus research
ResumoChronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8 + T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8 + T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8 + T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.
Referência(s)