Transfer of antigen-specific immunity after CD34+ cell enriched T cell-depleted peripheral blood stem cell transplantation and donor lymphocyte infusion

In an allogeneic peripheral blood stem cell transplantation (PBSCT) setting, either with or without CD34+ cell enrichment and T cell-depletion (n=4 or n=13, respectively), we studied the transfer of hepatitis B virus (HBV) specific immunity from electively immunized donors into HLA compatible recipients suffering from chronic myeloid leukemia (CML). For comparison, patients after bone marrow transplantation (n=7) were also analyzed. After excluding pre-existing HBV specific immunity in donor/recipient pairs, the prospective donors were vaccinated against HBV. Prior to transplantation, cellular and humoral HBV-specific immunity (proliferative responses towards HBspreS1-preS2 antigen and anti HBs titre) in donors of CD34+ cell enriched, unmanipulated and bone marrow grafts were in a similar range. Recipients were followed for up to 8 years after transplantation. Data from recipients who have been vaccinated after transplantation were excluded from analysis. Prior to donor lymphocyte infusion (DLI) - which was performed between 8 and 47 months post transplantation - cellular HBV immunity was significantly reduced (P = 0.003) after CD34+ cell enriched as compared to unmanipulated PBSCT (Figure 1). The strength of immune responses after CD34+ cell enrichment was similar to that after bone marrow transplantation. After DLI, cellular HBV immunity increased (mean values: 20556 vs. 1955 cpm increment) to levels similar to patients having received unmanipulated grafts. However, humoral HBV immunity was comparable after CD34+ cell enriched and unmanipulated PBSCT and did not increase after DLI. In conclusion, CD34+ cell enrichment and T cell-depletion led to a reduction of antigen-specific T cell responses which can most likely be explained by a 100-fold reduction of T cells as compared to unmanipulated grafts.