Stimulation through the TCR/CD3 complex up-regulates the CD2 surface expression on human T lymphocytes.
Despite the well known interrelationship between the CD2- and CD3-mediated signal transduction pathways, it is not well established whether the CD2 surface expression can be regulated by triggering of TCR/CD3 complex. In this study we show that the stimulation of human PBMC with the Cris-7 (CD3) mAb, both in soluble and particulate form, results in hyperexpression of the CD2 surface Ag, as assessed by immunofluorescence and semi-quantitative immunoprecipitation assays. Similar effects on CD2 surface expression were obtained when different CD3 mAb (OKT3, RW2-8C8 and Leu-4) were tested. The CD3-mediated CD2 up-regulation was suppressed by cycloheximide and actinomycin D, indicating that it requires de novo protein and RNA synthesis. In agreement with this, increased CD2 RNA levels were observed after 3 h of stimulation, reaching a plateau at 24 h that was maintained for 72 h. The CD2 up-regulation was concomitant to other CD3-induced activation-related events such as induction of surface CD25 and CD71 and high RNA levels for c-myc, IL-2R alpha- and beta-chains, CD71, and IFN-gamma. CD2 up-regulation appeared to be elicited by a protein kinase C-dependent mechanism because it was abrogated by staurosporine, a potent protein kinase C inhibitor. Moreover, IL-2-dependent events may also help in enhancing CD2 hyper-expression because it was only partially inhibitable by cyclosporine, dexamethasone, or Mar-108 (CD25) mAb. In conclusion, our data suggest that CD2 up-regulation can be a relevant event in T cell activation triggered by the physiologic engagement of the TCR/CD3 complex.
Alberola-Ila
J
J
Servei d'Immunologia, Hospital Clinic i Provincial de Barcelona, Spain.
Places
L
L
de la Calle
O
O
Romero
M
M
Yagüe
J
J
Gallart
T
T
Vives
J
J
Lozano
F
F
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000502:physiology*; D000954:Antigens, Surface / Q000096:biosynthesis; D018801:CD2 Antigens; D017252:CD3 Complex; D002455:Cell Division; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011493:Protein Kinase C