Different Types of Dendritic Cells Vary in Immune Activity

BUFFALO, NY--Dendritic cells play a critical role in the immune response to cancer and to the human immunodeficiency virus (HIV). Their function is to migrate to sites of inflammation, take up antigen, and present the antigen to T cells to create an immune response. [See related story on page 7.]

Researchers at the Ohio State University-James Cancer Hospital and Research Institute studied two different types of dendritic cells--those derived from CD34+ cells and those derived from monocytes/macrophages--to look for differences between these cells in mediating immune response.

"Our initial research shows that in mixed lymphocyte reactions and in presentation of soluble antigens, the monocyte/macrophage-derived dendritic cells are more potent than those derived from CD34+ cells. However, monocyte/macrophage-derived dendritic cells stimulate more interleukin-10 production, which may not be desirable," Pierre L. Triozzi, MD, associate professor of internal medicine, said at the Regional Cancer Center Consortium for Biological Therapy of Cancer meeting, hosted by Roswell Park Cancer Institute.

In these studies, the dendritic cells were derived from CD34+ hematopoietic progenitor cells, usually arising from the bone marrow, with tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), or from monocyte/macrophages, usually located in peripheral blood, with IL-4 and GM-CSF.

In other studies, the two types of dendritic cells were similar in their sensitivity to HIV infection, although the monocyte/macrophage-derived dendritic cells were more active immunologically, Dr. Triozzi said.

Both types of dendritic cells are able to express CD1a, which appears to be important in the presentation of certain antigens, he said. However, only the dendritic cells derived from CD34+ cells could produce significant numbers of CD1a+ dendritic cells in serum-free conditions. CD1a+ dendritic cells could be derived from the monocyte/macrophage dendritic cells only in the presence of fetal calf serum.

"The use of serum is not desirable in clinical studies, as it may alter the target antigen and lead to undesired immune responses against the serum itself," Dr. Triozzi said.

He noted that ongoing clinical studies are attempting to determine if the differences found in vitro between these two types of dendritic cells will influence their effects in vivo.