Mechanism of Anti-asialo GM1 Prevention of Graft-vs-Host Disease: Identification of Allo-antigen Activated T Cells

Abstract The purpose of this study was to begin to dissect the mechanism whereby anti-asialo GM 1 (αASGM 1 ) 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 αASGM 1 and αThy 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 αASGM 1 , the epitope recognized by αASGM 1 on GVHR T cells is an activation antigen. Because asialo GM 1 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 αASGM 1 infusions (T cells or macrophages). We compared the effects of αASGM 1 infusions on alloantigen-stimulated T-cell proliferation versus antigen presentation: T-cell proliferation was markedly reduced by αASGM 1 infusions, whereas antigen presentation function was not diminished. We conclude that the mechanism whereby αASGM 1 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.