K Nagaraju1, S R Naik, S Naik. 1. Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow.
Abstract
BACKGROUND: Chronic carriers of hepatitis B virus (HBV) have impairment of lymphoproliferative responses. Recently HBV infection of peripheral blood mononuclear cells (PBMC) has been reported. The defect in the proliferative capacity of carrier PBMC has not been correlated to the presence of HBV in these cells. METHODS: PBMC of fourteen HBV carriers and 14 healthy individuals were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM) or anti-CD3 for 3 days and with HBsAg and purified protein derivative (PPD) for 6 days. The supernatants of unstimulated and PHA-stimulated PBMC cultures were bioassayed for interleukin-2 (IL-2); the supernatants of unstimulated and lipopolysaccharide (LPS)-stimulated cultures were bioassayed for IL-1. DNA extracted from PBMC was hybridized with a 32P-labeled HBV probe to look for HBV DNA. RESULTS: HBV carriers' PBMC showed impaired responses to PHA, PWM and anti-CD3. No carrier demonstrated lymphoproliferative response to hepatitis B surface antigen (HBsAg). Seven of eight carriers with impaired HBsAg-specific proliferative responses who were tested for their response to an unrelated antigen showed a positive response to PPD. PBMC from HBV carriers produced similar amounts of IL-1 as normal PBMC on LPS stimulation; however, they produced significantly lower amounts of IL-2 as compared to normal PBMC under both spontaneous and PHA-stimulated conditions. HBV DNA was demonstrable in the PBMC of all fourteen carriers. CONCLUSIONS: The abnormal immune function found in chronic HBV carriers may be a consequence of replicative viral infection of the mononuclear cells.
BACKGROUND: Chronic carriers of hepatitis B virus (HBV) have impairment of lymphoproliferative responses. Recently HBV infection of peripheral blood mononuclear cells (PBMC) has been reported. The defect in the proliferative capacity of carrier PBMC has not been correlated to the presence of HBV in these cells. METHODS: PBMC of fourteen HBV carriers and 14 healthy individuals were stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM) or anti-CD3 for 3 days and with HBsAg and purified protein derivative (PPD) for 6 days. The supernatants of unstimulated and PHA-stimulated PBMC cultures were bioassayed for interleukin-2 (IL-2); the supernatants of unstimulated and lipopolysaccharide (LPS)-stimulated cultures were bioassayed for IL-1. DNA extracted from PBMC was hybridized with a 32P-labeled HBV probe to look for HBV DNA. RESULTS:HBV carriers' PBMC showed impaired responses to PHA, PWM and anti-CD3. No carrier demonstrated lymphoproliferative response to hepatitis B surface antigen (HBsAg). Seven of eight carriers with impaired HBsAg-specific proliferative responses who were tested for their response to an unrelated antigen showed a positive response to PPD. PBMC from HBV carriers produced similar amounts of IL-1 as normal PBMC on LPS stimulation; however, they produced significantly lower amounts of IL-2 as compared to normal PBMC under both spontaneous and PHA-stimulated conditions. HBV DNA was demonstrable in the PBMC of all fourteen carriers. CONCLUSIONS: The abnormal immune function found in chronic HBV carriers may be a consequence of replicative viral infection of the mononuclear cells.