CD 14⁺ suppressor cells in mobilized stem cell products

Immune function is a balance of positive and negative immunoregulatory cells. We report the characterization of a suppressor cell activity in mobilized peripheral blood stem cell (PSC) products. These cells are low density, non-adherent, phagocytic and CD 14⁺. PSC products are used with increasing frequency following high dose therapy and stem cell rescue. Compared to bone marrow (BM) products PSC can accelerate hematopoietic recovery, contain fewer tumor cells and may prolong survival, perhaps due to a more rapid immune reconstitution. Both BM and PSC products have increased cytokine levels (RT-PCR) with a predominate TH-2 profile compared to normal peripheral blood leukocytes (PBL). Significant differences in T and B cell phenorypes are observed with a trend for heightened numbers of B cells and PMN's in BM and T and CD14⁺ cells in PSC products. Functionally, the PSC products have increased NK and suppressor cell activity compared to BM cells. The phytobemagglutinin (PHA) response for both the BM and PSC products are significantly depressed compared to normal PBL The addition of irradiated PSC cells can suppress allo T cell expansion in IL-2 and PHA, IL-2 and 1L-12 mitogenesis. The mechanism of suppression by the CDI4⁺ cells does not cross transwell plates but can kill 3H-thymidine-labeled allogcnic T cell blasts in a time and dose dependent manner suggesting a need for cell-cell contact. We suggest that the suppressor cell is a monocyte or monocyte-dendritic cell precursor with significant potential to regulate immune recovery following normal or myeloablative therapy, immunotherapy, as well as to prevent graft verses host disease in allogeneic transplant patients.