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© Research
Publication : eLife

Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 14 Nov 2015

Alanio C, Nicoli F, Sultanik P, Flecken T, Perot B, Duffy D, Bianchi E, Lim A, Clave E, van Buuren MM, Schnuriger A, Johnsson K, Boussier J, Garbarg-Chenon A, Bousquet L, Mottez E, Schumacher TN, Toubert A, Appay V, Heshmati F, Thimme R, Pol S, Mallet V, Albert ML,

Link to Pubmed [PMID] – 26568315

Link to DOI [DOI] – 10.7554/eLife.07916e07916

Elife 2015 Nov; 4():

Chronic 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.

https://pubmed.ncbi.nlm.nih.gov/26568315