Mechanism of anti-asialo GM1 prevention of graft-vs-host disease: identification of allo-antigen activated T cells.
The purpose of this study was to begin to dissect the mechanism whereby anti-asialo GM1 (alpha ASGM1) prevents otherwise lethal graft-vs-host disease (GVHD) across multiple minor histocompatibility barriers in mice. Phenotypic characterization of cells from the peak proliferative time of the graft-vs-host reaction (C57BL/6J lymph node cells----irradiated LP/J, days 5-7) revealed the alpha ASGM1 and alpha Thy 1.2 identified cells with an approximate 80% concordance and that NK-1.1 staining was negligible. Because resting T cells do not label with alpha ASGM1, the epitope recognized by alpha ASGM1 on GVHR T cells is an activation antigen. Because asialo GM1 has been previously found on the surface of activated macrophages, we wanted to distinguish between the two most likely targets for the in vivo effect of alpha ASGM1 infusions (T cells or macrophages). We compared the effects of alpha ASGM1 infusions on alloantigen-stimulated T-cell proliferation versus antigen presentation: T-cell proliferation was markedly reduced by alpha ASGM1 infusions, whereas antigen presentation function was not diminished. We conclude that the mechanism whereby alpha ASGM1 prevents GVHD does not involve NK cells or antigen presenting cells, but does involve activated donor T cells. The potential therapeutic advantage of such an antibody for use in human disorders compared to pan-immunosuppression lies in its ability to eliminate selectively those T cells involved in the immunologic process (i.e. activated T cells) while sparing the remainder of the T-cell repertoire.
Charley
M R
MR
Department of Dermatology, University of Pittsburgh School of Medicine, PA.
Mikhael
A
A
Hackett
J
J
Kumar
V
V
Bennett
M
M
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; D006028:Glycosphingolipids; D007519:Isoantigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside