Nature of immunological non-responsiveness to hepatitis B vaccine in healthy individuals.
This study was undertaken in order to analyse the immuno-regulatory mechanism of non-responsiveness to hepatitis B (HB) vaccine in healthy individuals. We have reported already that peripheral mononuclear cells (MNC) isolated from anti-HBs sero-positive subjects after booster injection are able to make anti-HBs in vitro by stimulation with pokeweed mitogen (PWM) plus HBsAg. In contrast, under the same conditions, non-responder (NR) MNC failed to produce anti-HBs in vitro, even after an additional injection, although an amount of immunoglobulin was synthesized corresponding with the responder controls. Co-culture experiments carried out with T-cell fractions (T) and non-T-cell fractions (NT) from NR and controls showed: (i) by Week 2 after the last vaccination, NT from NR could hardly be activated to produce anti-HBs; however, by Week 4 significant synthesis of anti-HBs was induced by the stimulation of responder T; (ii) in experiments using responder NT and T from NR, seven out of eight and five out of nine co-cultures were found to make anti-HBs by Weeks 2 and 4, respectively; (iii) T from NR, as well as their culture supernatants, specifically suppressed anti-HBs production of responder MNC, especially by Week 4 after the last vaccination. From these results, it is predicted that the early stage of non-responsiveness in NR is mainly due to a defect of the B-cell repertoire, while that of the late stage is caused by the existence of HBsAg-specific suppressor T cells.
Chiou
S S
SS
Division of Medicine, Tokyo Women's Medical College, Japan.
Yamauchi
K
K
Nakanishi
T
T
Obata
H
H
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D008211:Lymphocyte Cooperation; D008297:Male; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D011043:Pokeweed Mitogens; D014761:Viral Hepatitis Vaccines