Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo.
The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.
Nickoloff
B J
BJ
Department of Pathology, University of Michigan, Ann Arbor.
Mitra
R S
RS
Lee
K
K
Turka
L A
LA
Green
J
J
Thompson
C
C
Shimizu
Y
Y
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D018122:B7-1 Antigen; D001483:Base Sequence; D015152:Blotting, Northern; D018106:CD28 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002461:Cell Line, Transformed; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D015603:Keratinocytes / Q000378:metabolism*; D008024:Ligands; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D018106:CD28 Antigens; D015815:Cell Adhesion Molecules; D008024:Ligands; D015335:Molecular Probes; D018799:Intercellular Adhesion Molecule-1