Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B.
OBJECTIVE
Chronic hepatitis B (CHB) infection acquired perinatally or in early childhood has been associated with a prolonged phase of immune tolerance from viral exposure into early adulthood. The immune-tolerant phase of the disease is characterized by high levels of hepatitis B virus (HBV) DNA and normal liver biochemistry, with minimal or no fibrosis. We investigated whether the age of patients with CHB affects their antiviral immunity and whether children and young adults have a veritable state of immunologic tolerance.


METHODS
We isolated T cells from different age groups of patients with CHB and used flow cytometric methods to measure production of effector and inflammatory cytokines (interferon, tumor necrosis factor, interleukin [IL]-17A, IL-22, and IL-8), T-helper (Th)2 cytokines (IL-10, IL-4), Th1 cytokines (IL-2 and IL-21), and the CC chemokine CCL3 (MIP-1). We also measured markers of T-cell exhaustion or inhibition (PD-1, LAG-3, TIM3, LAIR-1, and CTLA-4) and HBV-specific T cells.


RESULTS
Young patients with CHB have a Th1-cell cytokine profile and a partial profile of T-cell exhaustion. Direct quantification of the HBV-specific T-cell response showed that young patients with CHB have more HBV-specific T cells with the ability to proliferate and produce cytokines than adult patients with CHB.


CONCLUSIONS
HBV infection in younger patients is not associated with an immune profile of T-cell tolerance. On the contrary, children and young adults with chronic HBV infection have an HBV-specific immune profile that is less compromised than that observed in older patients.
Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, London, England.
Patrick T F
PTF
Kennedy
Infection & Immunity Program, Singapore Institute for Clinical Sciences, A*STAR, Singapore.
Elena
E
Sandalova
Infection & Immunity Program, Singapore Institute for Clinical Sciences, A*STAR, Singapore.
Juandy
J
Jo
Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, London, England.
Upkar
U
Gill
Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, London, England.
Ines
I
Ushiro-Lumb
Infection & Immunity Program, Singapore Institute for Clinical Sciences, A*STAR, Singapore.
Anthony T
AT
Tan
Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, London, England.
Sandhia
S
Naik
Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, London, England.
Graham R
GR
Foster
Infection & Immunity Program, Singapore Institute for Clinical Sciences, A*STAR, Singapore; Program Emerging Viral Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: antonio@sics.a-star.edu.sg.
Antonio
A
Bertoletti
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology; D008131:London; D008213:Lymphocyte Activation; D008297:Male; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D004279:DNA, Viral; D018836:Inflammation Mediators