Contributions of the CD2 and CD28 T lymphocyte activation pathways to the regulation of the expression of the colony-stimulating factor (CSF-1) gene.
The T cell adhesion molecule CD28 provides a costimulatory signal, in combination with either CD2 or CD3 mAb. CD28 appears to regulate the expression, by T cells, of cytokines normally produced by accessory cells, namely IL-1 alpha, TNF-alpha, and CSF-1. The CSF-1 gene is expressed as a 4.0-kb transcript by human T cells activated with mAb directed against CD2 and CD28, alone or in combination. A kinetic analysis of its expression showed low steady-state levels of the transcript after CD2 stimulation, and a transient rise after CD28 stimulation. In contrast, a mean fivefold increase in the levels of the transcript was detected in CD2 plus CD28-stimulated cells. The potential mechanisms regulating this increase were investigated. The half-life of the CSF-1 transcript was identical in cells activated with either CD28 or CD2 plus CD28. Transcription of the CSF-1 gene appeared to undergo attenuation in resting cells as well as in cells activated via a single pathway; this attenuation was relieved in part by the combined CD2 plus CD28 stimulation. Thus in vitro costimulation via the CD2 and CD28 molecules regulates the expression of the CSF-1 gene mainly at the transcriptional level.
Unité 119 de l'INSERM, Marseille, France.
C
C
Cerdan
D
D
Razanajaona
Y
Y
Martin
M
M
Courcoul
C
C
Pavon
C
C
Mawas
D
D
Olive
F
F
Birg
D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D018106:CD28 Antigens; D005786:Gene Expression Regulation; D016236:Genes, fms; D006801:Humans; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor