Expression of interleukin-10 in isolated CD8+ T cells and monocytes from growth factor-mobilized peripheral blood stem cell products: a mechanism of immune dysfunction.
Previous reports showed the abnormal activation of immune cells in growth factor-mobilized peripheral blood stem cell (PBSC) products, which might be responsible for depressed T cell responsiveness to mitogens compared with normal peripheral blood mononuclear cells (PBMC). In the present study, the mRNA expression levels of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) were significantly higher in CD4+ and CD8+ T cells from mobilized PBSC products compared with CD4+ and CD8+ cells from normal peripheral blood (PB). The mRNA expression levels of IL-4 and IL-10 were significantly higher in CD8+ compared with CD4+ cells from PBSC products. However, the expression of IL-2 and IFN-gamma mRNA transcripts was similar in the CD4+ and CD8+ T cells from PBSC products. The levels of IL-10, IL-8, and tumor necrosis factor (TNF)-alpha mRNA were also significantly higher in monocytes isolated from PBSC products compared with monocytes isolated from normal PB. Expression of IL-10-specific mRNA in monocytes also was significantly higher than the levels observed in CD8+ cells from PBSC products. We suggest that both CD4+ and CD8+ cells in the PBSC products are highly activated. However, their response to phytohemagglutinin (PHA) mitogenesis is depressed in part because of IL-10 expression by CD8+ cells and monocytes in addition to the higher levels of monocyte-dependent T cell inhibitory activity. These data demonstrate that aberrant IL-10 expression in the CD8+ T cells and monocytes present in PBSC products may represent a possible mechanism of immune dysfunction in patients after high-dose chemotherapy (HDT) and peripheral blood stem cell transplantation (PBSCT).
Varney
M L
ML
Department of Pathology and Microbiology, The University of Nebraska Medical Center, Omaha 68198-5660, USA.
Ino
K
K
Ageitos
A G
AG
Heimann
D G
DG
Talmadge
J E
JE
Singh
R K
RK
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002469:Cell Separation; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007154:Immune System Diseases / Q000097:blood*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D014158:Transcription, Genetic
D016207:Cytokines; D006133:Growth Substances; D010835:Phytohemagglutinins; D016753:Interleukin-10