T-lymphocyte function from peripheral blood stem-cell donors is inhibited by activated granulocytes

Area of Science:

• Immunology
• Hematology
• Transplantation Medicine

Background:

• Peripheral blood stem cell (PBSC) transplants yield more T cells than bone marrow transplants (BMT).
• Despite T cell count differences, acute graft-versus-host disease (GvHD) incidence and severity are similar between BMT and PBSC recipients.
• Lymphokine profile differences are hypothesized to explain similar clinical outcomes in BMT and PBSCT.

Purpose of the Study:

• To investigate the immunological differences between peripheral blood mononuclear cells (PBMC), G-CSF mobilized PBMC (G-PBMC), and bone marrow mononuclear cells (BM-MC).
• To determine the role of lymphokine profiles and cellular composition in acute GvHD following different transplant types.
• To explore the mechanism behind the similar incidence of acute GvHD in BMT and PBSCT.

Main Methods:

• Flow cytometry and ELISA were used to analyze gamma-interferon (IFN) and IL-4 production.
• Hematoxylin and eosin staining assessed cell morphology.
• Annexin/propidium iodide staining evaluated apoptosis.

Main Results:

• G-PBMC exhibited significantly decreased ex vivo production of gamma-IFN (85%) and IL-4 (60%) compared to PBMC and BM-MC.
• Fresh G-PBMC comprised 85% low-density granulocytes (LDGs) that underwent apoptosis after 48 hours in culture, coinciding with gamma-IFN production recovery.
• In vitro, G-CSF induced granulocyte to LDGs conversion, which inhibited T-cell function via H2O2 production, not Th2-type immune deviation.

Conclusions:

• The number of Th1 and Th2 cells infused in BMT and PBSCT do not significantly differ.
• The high number of infused granulocytes and progenitors in PBSCT may contribute to the observed low incidence of acute GvHD.
• Granulocytes show potential for short-term immunosuppressive therapy, with ongoing investigations in mouse models.