Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.
The proliferative responsiveness of granulocyte colony-stimulating factor (G-CSF)-mobilized blood was studied in uni-directional mixed leukocyte cultures. Unfractionated mononuclear cells from mobilized blood obtained by leukapheresis at day 4 after initiation of G-CSF (G-PBMC) were hyporesponsive (31.5% +/- 9.2% response, P = .003) compared to mononuclear cells obtained from the peripheral blood before administration of G-CSF (preG-PBMC). There was great variability among donors when purified preG- and G-CD4 cells were compared. In eight of 10 donors, G-CD4 cells were equally responsive or moderately hyporesponsive; in two of 10 donors, G-CD4 cells were more strikingly hyporesponsive. CD14 cells derived from leukapheresis products (G-CD14 cells) suppressed alloantigen-induced proliferation by 48.6% +/- 7.5% when added to preG-PBMC or preG-CD4 cells at responder-CD14 ratios of 2:1 (P < .001). Suppression was evident (14.4% +/- 5.0%) even at responder-CD14 ratios of 8:1 and was largely contact-independent. PreG- and G-CD14 cells had equivalent potency in suppressing proliferative responses. Given that G-CSF-mobilized blood cell grafts contain 50-fold more CD14 cells and only 10-fold more T cells than marrow, we propose that suppression of donor T cells by the large proportion of monocytes present in leukapheresis products could contribute to the unexpectedly low incidence and severity of graft-versus-host disease after peripheral blood stem cell transplantation.
Mielcarek
M
M
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Martin
P J
PJ
Torok-Storb
B
B
D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D007519:Isoantigens; D018950:Lipopolysaccharide Receptors; D016179:Granulocyte Colony-Stimulating Factor