The purpose of this study was to begin to dissect the mechanism whereby anti-asialo GM₁ (αASGM₁) 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 αASGM₁ 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 αASGM₁ the epitope recognized by αASGM₁ 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 αASGM₁ infusions (T cells or macrophages). We compared the effects of αASGM₁ infusions on alloantigen-stimulated T-cell proliferation versus antigen presentation: T-cell proliferation was markedly reduced by αASGM₁ infusions, whereas antigen presentation function was not diminished. We conclude that the mechanism whereby αASGM₁ 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.