Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen

Some human subjects vaccinated with hepatitis B surface antigen (HBsAg) do not produce antibodies to the vaccine (nonresponders). The mechanism for no nresponse is unknown. To understand the response and nonresponse to nominal antigens better, we determined the level and kinetics of cytokine secretio n in response to HBsAg and tetanus toroid (TT) by peripheral blond mononucl ear cells (PBMC) in vitro from HBsAg vaccine responders and nonresponders a nd from individuals naive to HBsAg, Proliferating PBMC secreted peak levels of interleukin-2 (IL-2) at 2 days and peak levels of tumor necrosis factor -beta (TNF-beta), interferon-gamma (IFN-gamma), IL-4 and IL-10 at 3-6 days post-stimulation. In contrast, nonproliferating PBMC (whether from nonrespo nders, naive subjects or weak responders) did not produce detectable levels of TNF-beta or IFN-gamma, nor was IL-4 or IL-10 produced significantly, an d that produced had a different kinetic profile from that of proliferating PBMC. HBsAg-specific cytokine production by PBMC from strong responders bro adly paralleled their cytokine responses to TT. Cellular cytokine mRNA leve ls measured by reverse transcriptase-polymerase chain reaction corroborated the secreted cytokine results. The anti-HBsAg- and anti-TT-specific T cell cytokine responses were mixed Th-1/2-like and donor-specific. An HBsAg-spe cific cytokine response, but not a TT-specific cytokine response, was compl etely missing in nonresponders. These data suggest that the T cell defect o f HBsAg nonresponse is not due to a skewed cytokine profile. (C) 2000 Elsev ier Science Ltd. All rights reserved.