CXCR5+CD8+T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection.
Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5+CD8+T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5+CD8+T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5+CD8+T cells in peripheral blood, in which CXCR5+CD8+T cells were negatively correlated with the frequency of CXCR5+CD4+T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5+CD8+T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5-CD8+T cells. Unlike CXCR5+CD4+T cells, when incubated with naive CD19+CD27-B cells, CXCR5+CD8+T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5+CD8+T cells in B cell-CXCR5+CD4+T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5+CD8+T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5+CD8+T cells tended to associate with low HBV DNA load, and the frequency of CXCR5+CD8+T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5+CD8+T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.
1 Department of Hepatobiliary Surgery, Kunming General Hospital of PLA , Kunming, China .
Hang
H
Jiang
2 Department of The First General Surgery, The First People's Hospital of Yunnan Province , Kunming, China .
Linhai
L
Li
3 Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province , Kunming, China .
Jiang
J
Han
3 Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province , Kunming, China .
Zhiwei
Z
Sun
4 Hepatocellular Carcinoma Diagnosis and Research Center, Beijing 302 Hospital , Beijing, China .
Yihui
Y
Rong
3 Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province , Kunming, China .
Yun
Y
Jin
D000410:Alanine Transaminase / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000821:virology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D008297:Male; D054380:Receptors, CXCR5 / Q000032:analysis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019562:Viral Load
C095085:CXCR5 protein, human; D016207:Cytokines; D054380:Receptors, CXCR5; D000410:Alanine Transaminase
CXCR5+ CD8+ T cell; chronic hepatitis B