Peripheral blood dendritic cells and GM-CSF as an adjuvantfor hepatitis B vaccination in hemodialysis patients

Abstract

Dysfunctional antigen presentation may underlie the impaired antibody response to hepatitis B vaccination in hemodialysis patients. Dendritic cells are considered to be the most important antigen presenting cells, but their presence and function in hemodialysis patients is unclear. Granulocyte-monocyte-colony stimulating factor (GM-CSF) has been given successfully to hemodialysis patients to increase the proportion of responders to hepatitis B vaccination. Although GM-CSF acts on both monocytes and dendritic cells, the mechanisms underlying its adjuvant quality are largely unknown. In this study we analyzed monocytes and dendritic cells in the peripheral blood of hemodialysis patient that had responded to a standard hepatitis B vaccination procedure (responders), patients who had not responded (nonresponders), and healthy controls. The nonresponders were given two additional booster vaccines, both preceded by administration of GM-CSF the day before. After two booster vaccinations with GM-CSF, six out of seven patients developed a protective antibody response to hepatitis B. The memory T-cell response to tetanus toxoid was significantly lower in nonresponders compared to controls. The monocytes of dialysis patients and healthy controls showed a similar expression of relevant cell surface molecules. However, the numbers of circulating dendritic cells were on average 50% reduced compared to healthy controls, with a further reduction after GM-CSF administration. This was accompanied by a decrease of T-cell proliferation in antigen presentation assays. Monocytes showed increased major histocompatibility complex (MHC) class II, CD54, and CD40 expression, while their antigen-presenting capacity remained unchanged. GM-CSF is an effective adjuvant for hepatitis B vaccination in primary nonresponding hemodialysis patients, but paradoxically decreases the antigen presenting capacity of peripheral blood mononuclear cells and the number of circulating dendritic cells.