Impaired induction of the CD28-responsive complex in granulocyte colony-stimulating factor mobilized CD4 T cells.
Use of the CD28/B7 costimulatory signal for T-cell activation was analyzed in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (G-PBMCs) and in peripheral blood mononuclear cells obtained before administration of G-CSF (preG-PBMCs). CTLA4Ig inhibition of OKT3-stimulated proliferation was significantly lower in G-PBMCs compared with preG-PBMCs (39.9% +/- 5.6% and 72.2% +/- 5.4%, respectively; P < .001). Furthermore, as shown in electrophoretic mobility-shift assays, the inducible level of the T-cell transcription factor CD28 responsive complex (CD28RC) was suppressed in CD4 cells derived from G-PBMC. However, depletion of CD14 cells from G-PBMCs restored CD28RC induction to normal levels. Taken together, these findings suggest that the large number of CD14 monocytes in G-PBMCs may limit T-cell responsiveness by suppressing the induction of the CD28RC.
Tanaka
J
J
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Mielcarek
M
M
Torok-Storb
B
B
D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D060908:CTLA-4 Antigen; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000235:genetics; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D016853:Muromonab-CD3 / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D014158:Transcription, Genetic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004268:DNA-Binding Proteins; D018796:Immunoconjugates; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D016853:Muromonab-CD3; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D000069594:Abatacept