HUMORAL AND CELLULAR IMMUNE-RESPONSES TO HEPATITIS-B VACCINATION IN HEPATITIS-B SURFACE ANTIGEN-CARRIER CHILDREN WHO CLEARED SERUM-HEPATITIS-B SURFACE-ANTIGEN

The immune responses to hepatitis B vaccine were studied in 11 hepatit is B surface antigen (HBsAg) carrier children who had cleared HBsAg bu t failed to develop hepatitis B surface antigen antibodies (anti-HBs) in sera (group 1), 5 HBsAg carrier children who had cleared HBsAg and developed detectable anti-HBs in sera (group 2), and 5 healthy subject s seronegative for all hepatitis B virus (HBV) markers (group 3), Afte r receiving three doses of HB vaccine, group 1 subjects failed to deve lop detectable anti-HBs, Subsequently, each subject of the three group s was given one dose of the same vaccine for a cellular immunity study , and a measurable proliferation of peripheral blood mononuclear cells (PBMC) to HBsAg was detected in 1 of 8 (12.5%), 0 of 5, and 4 of 5 (8 0%) of the cases in each group, respectively, after vaccination, The r emoval of CD8(+) cells enhanced the HBsAg blastogenic response in grou p 3 but did not reverse the unresponsiveness in group 1 and group 2 su bjects, The addition of interleukin (IL)-2 in culture reversed unrespo nsiveness in all cases except one case in group 1, Compared with befor e vaccination, PBMC from group 2 subjects produced significantly less interferon gamma (IFN-gamma) and more IL-4 in response to HBsAg after vaccination, a cytokine response not observed in group 1 subjects, HLA typing indicated that 3 of 10 patients in group 1 (30%) and 1 of 5 pa tients in group 2 (20%) had HLA-DRw14-DRw52, a marker previously linke d to low anti-HBs response to hepatitis B vaccine in Taiwan, We conclu de that the underlying causes of poor anti-HBs response in group 1 sub jects are multifactorial, including specific failure of antigen presen tation or T-cell activation, or the lack of T helper (Th)2 cell-like r esponse to HBsAg, HLA-DRw14-DRw52 does not confer absolute nonresponsi veness to HBsAg, These patients are not benefited by hepatitis B immun ization.