Single-cell analysis of costimulation by B cells, endothelial cells, and fibroblasts demonstrates heterogeneity in responses of CD4(+) memory T cells.
Human endothelial cells (EC) express MHC class II molecules in vivo and are likely to be involved in presentation of antigens to CD4(+) T cells. We examined, at the single-cell level, EC presentation of superantigens to resting CD4(+) memory T cells. Within 2 h of adherence to class II+ EC early T cell activation is evidenced by translocation of nuclear factor of activated T cells (NFAT), surface expression of CD69, and synthesis of IFN-gamma and IL-2. Naive T cells are not activated. T cell activation is dependent on the prior induction of MHC class II molecules on EC and is blocked by antibodies to LFA-3 (CD58). Our data place EC along a spectrum of antigen-presenting ability. Activated B cells and macrophages trigger more cells to express cytokines than do EC and at lower antigen concentrations; EC are in turn, superior to fibroblasts or smooth muscle cells. Furthermore, the concept of activation thresholds for cytokine synthesis within T cells also extends to earlier activation events: NFAT translocation is relatively easy to trigger, as is CD69 expression; fewer cells can be triggered to express IFN-gamma and fewer still to express IL-2. EC may, therefore, contribute to a graded immune response by inducing qualitatively and quantitatively different responses than professional APC.
Murphy
L L
LL
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, 92697, USA.
Mazanet
M M
MM
Taylor
A C
AC
Mestas
J
J
Hughes
C C
CC
D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D018448:Models, Immunological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D017493:Leukocyte Common Antigens