Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Abatacept
-
Adult
-
Antigens, CD
-
Antigens, Differentiation / pharmacology
-
B7-1 Antigen / immunology*
-
CD28 Antigens / immunology*
-
CD4-Positive T-Lymphocytes / drug effects*
-
CD4-Positive T-Lymphocytes / immunology
-
CTLA-4 Antigen
-
DNA-Binding Proteins / biosynthesis*
-
DNA-Binding Proteins / classification
-
DNA-Binding Proteins / genetics
-
Gene Expression Regulation*
-
Granulocyte Colony-Stimulating Factor / pharmacology*
-
Hematopoietic Stem Cell Mobilization
-
Humans
-
Immunoconjugates*
-
Interleukin-2 / genetics
-
Leukapheresis
-
Leukocytes, Mononuclear / immunology*
-
Leukocytes, Mononuclear / metabolism
-
Lipopolysaccharide Receptors / analysis
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / physiology*
-
Lymphocyte Culture Test, Mixed
-
Muromonab-CD3 / pharmacology
-
Promoter Regions, Genetic / genetics
-
Regulatory Sequences, Nucleic Acid*
-
Transcription Factors / biosynthesis*
-
Transcription Factors / classification
-
Transcription Factors / genetics
-
Transcription, Genetic
Substances
-
Antigens, CD
-
Antigens, Differentiation
-
B7-1 Antigen
-
CD28 Antigens
-
CTLA-4 Antigen
-
CTLA4 protein, human
-
DNA-Binding Proteins
-
Immunoconjugates
-
Interleukin-2
-
Lipopolysaccharide Receptors
-
Muromonab-CD3
-
Transcription Factors
-
Granulocyte Colony-Stimulating Factor
-
Abatacept