Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood.
The T cell-mediated antineoplastic activity observed following allogeneic transplantation and the suggestion of improved therapeutic efficacy by autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) stimulated our interest in the immunologic competence of stem cell products. We report the immune phenotype and function of normal peripheral blood (PB) cells, bone marrow (BM) cells from normal donors and cancer bearing patients, GM-CSF-mobilized and apheresed blood mononuclear cells from NHL patients, unmobilized apheresed mononuclear cells from normal volunteers and umbilical cord blood (CB). The analyses include three-color fluorescent cytometry of the major hematologic and immunologic phenotypes as well as natural killer (NK) activity, natural suppressor (NS) activity, and phytohemagglutinin (PHA) and pokeweed (PWM) mitogenesis. These studies demonstrated an increased frequency of T cells in apheresis products as compared to BM and CB products. Specifically, the mobilized PSC had significant increases in CD3+, CD4+, CD45RO+ and CD56+ cells relative to BM cells. In addition, the frequency of TCR gamma/delta + cells in all the stem cell products, with the exception of CB, were also increased compared to normal peripheral blood leukocytes (PBL). However, all the stem cell products had a significant depression in T (PHA mitogenesis) and B (PWM mitogenesis) cell function. The depression in immune cell functionality, in the PSC products was perhaps due to the high frequency of monocytes which appeared to be increased due to both mobilization and apheresis. The frequency of the NK cell phenotype (CD56) but not function was increased in the mobilized PSC products, while the NK cell function in the BM products from cancer patients but not normal donors was depressed as compared to normal PBL. In summary, there are significant differences in the cellular phenotypes and immunologic competence among the various stem cell products with potential therapeutic implications.
Mills
K C
KC
Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Gross
T G
TG
Varney
M L
ML
Heimann
D G
DG
Reed
E C
EC
Kessinger
A
A
Talmadge
J E
JE
D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D007937:Leukapheresis; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology / Q000473:pathology; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D008934:Mitogens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor