title: Circulating CD4+CD25high regulatory T cells and expression of PD-1 and BTLA on CD4+ T cells in patients with chronic hepatitis B virus infection.
abstract: The roles of regulatory T cells (Tregs) and PD-1 in hepatitis B have not been clearly described. Also, the role of B and T lymphocyte attenuator (BTLA), which serves as a negative regulator of T-cell activation, is still unknown in hepatitis B. In this study, we analyzed the frequency of circulating CD4(+)CD25(high) Tregs in patients with chronic hepatitis B (CHB), and subsequently investigated expression of PD-1 and BTLA on CD4(+) T cells, as well as their relationships with the clinical index of CHB patients. A total of 39 CHB patients and 19 healthy persons as controls were enrolled in the study. We found that the frequency of CD4(+)CD25(high) Tregs and PD-1 expression on CD4(+) T cells was significantly increased in CHB patients compared with normal controls. However, BTLA expression on CD4(+) T cells showed no significant difference between the two groups. The frequency of Tregs was significantly higher in patients with HBV DNA titers >or=10(8) than in those with HBV DNA titers <10(8). Circulating CD4(+)CD25(high) Treg frequency and PD-1 expression on CD4(+) T cells correlated positively with serum HBV DNA load in CHB patients. Our findings suggest that the increased frequency of CD4(+)CD25(high) Tregs and PD-1 expression on CD4(+) T lymphocytes may inhibit the cellular immune response against HBV and affect viral clearance, leading to the persistence of chronic HBV infection.
authors.affiliation: Center of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Nan
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Sun
authors.forename: Jiu-Ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Bai
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015870:Gene Expression; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C482586:BTLA protein, human; D015704:CD4 Antigens; D004279:DNA, Viral; D053645:Interleukin-2 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic