Endothelial cells augment T cell interleukin 2 production by a contact-dependent mechanism involving CD2/LFA-3 interaction.
We have demonstrated that endothelial cells (EC) augment IL-2 production by PHA-stimulated PBMC or purified CD4+ T cells and that the increase is apparent both in the amount of soluble IL-2 secreted and in the level of specific mRNA detectable by Northern blot hybridization. The ability of EC to affect levels of IL-2 cannot be reproduced by soluble factors, including the cytokines IL-1, IL-6, IFN-gamma, or TNF, conditioned medium from resting EC or IL-1, IFN-gamma- or TNF-treated EC, or from resting PBMC + EC cultures. Separation of the EC and PBMC by a Transwell membrane demonstrated that cell contact was required for augmentation of IL-2 synthesis and that this effect was unlikely to be mediated by a short-lived soluble signal. The cell-cell interaction required the ligand pair CD2/LFA-3, since augmentation could be inhibited by antibodies to these structures. Antibodies to ICAM-1, LFA-1, CD4, and MHC class II were without effect. A contact-dependent pathway involving CD2/LFA-3 interactions also may be used by EC to augment IL-2 production from T cells stimulated more specifically through the TCR/CD3 complex with antibody OKT3. This pathway provides a proliferative advantage to T cells stimulated with OKT3 in the presence of EC and may also be involved in the proliferative response of resting T cells to allogeneic class II MHC-expressing EC. We propose that EC augmentation of T cell IL-2 synthesis may be critical in the ability of EC to elicit primary T cell antigen responses and may have consequences for the development of localized cell-mediated immune reactions.
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
C C
CC
Hughes
C O
CO
Savage
J S
JS
Pober
D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000032:analysis; D018968:CD58 Antigens; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011971:Receptors, Immunologic / Q000276:immunology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D015704:CD4 Antigens; D018968:CD58 Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic