The LFA-3 adhesion pathway is differently utilized by superantigen-activated human CD4+ T-cell subsets.
The superantigen SEA binds to MHC class II molecules and activates a large fraction of T cells as a result of interaction with particular TCR-V beta sequences. MHC class II transfected CHO cells induce a marginal CD4+ T-cell proliferation in the presence of SEA. CHO cells transfected with both MHC class II and LFA-3 (HLA-DR4/LFA-3 double transfectants) supported a vigorous T-cell proliferation and required 1000-fold lower SEA concentration than DR4-transfected cells. DR4/LFA-3 double transfectants presenting SEA to CD4+ T cells induced large amounts of IFN-gamma, while single DR4 transfectants failed to elicit IFN-gamma production. CD4+45RA+ naive T cells proliferated much more strongly compared with CD4+45R0+ memory T cells when SEA was presented by the DR4/LFA-3-transfected cells. In contrast, IFN-gamma production was only detected in CD4+45R0+ memory cells. The enhanced proliferation by the CD4+45RA+ naive T cells was not due to a stronger binding to the accessory DR4/LFA-3 cells. Human CD4+ T-cell lines mediated a low level of SEA-dependent cell-mediated cytotoxicity (SDCC) against DR4 target cells, whereas a strong SDCC was mediated against DR4/LFA-3-expressing target cells. These results demonstrate that superantigen-activated human CD4+ T cells require the adhesion molecule LFA-3 for optimal stimulation and that the CD4+ naive and memory T-helper cells are different in their response to LFA-3 as an accessory molecule.
Gjörloff
A
A
Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Sweden.
Hedlund
G
G
Kalland
T
T
Sansom
D
D
Fischer
H
H
Trowsdale
J
J
Sjögren
H O
HO
Dohlsten
M
M
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018968:CD58 Antigens; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology*
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D004768:Enterotoxins; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C026066:enterotoxin A, Staphylococcal