Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease.
Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.
Ellies
L G
LG
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Jones
A T
AT
Williams
M J
MJ
Ziltener
H J
HJ
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry*; D018952:Antigens, CD34; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D015854:Up-Regulation
D015703:Antigens, CD; D018952:Antigens, CD34; D009844:Oligosaccharides; D016695:Glycosyltransferases