CD3+ T Cells in Severe Combined Immunodeficiency (SCID) Mice. V. Allogeneic T Cells Engrafted into SCID Mice Do Not Induce Graft‐Versus‐Host Disease in spite of the Absence of Host Veto and Natural Suppressor Cell Activity

Abstract

Intravenous injection of 10(6) to 10(7) non-fractionated spleen cells (SC) from C57BL/6 (B6, H-2b) mice into completely allogeneic, immunodeficient H-2d severe combined immuno deficiency (scid) mice leads to engraftment of allogeneic donor T cells. Mice analysed in the tenth week posttransfer had engrafted donor-type CD4+ and CD8+ T cells in the spleens but showed no clinical evidence of graft-versus-host disease (GVHD). Transfer of allogeneic T cells engrafted in scid recipients did not induce GVHD upon i.v. injection into secondary scid recipients and lead in most recipients to engraftment of a pure CD4+ T-cell population. Experiments were carried out to investigate the reason(s) for the lack of GVHD in recipient scid mice, i.e. the presence of allotolerance in the engrafted donor T cells. Scid spleen cells (SC) efficiently stimulated alloreactive responses of B6 T cells: scid SC stimulated H-2d-specific cytotoxic responses in a B6 anti-scid mixed lymphocyte culture in vitro, and scid SC injected i.v. into B6 mice efficiently primed splenic cytotoxic lymphocyte precursors against H-2d alloantigens. Moreover when assayed in vitro, no veto activity or natural suppressor activity was detectable in scid SC. These data demonstrate that tolerizing mechanisms currently believed to operate in vivo can not explain the fact that allogeneic T cells injected i.v. into immunodeficient scid mice become tolerized against host-type alloantigens. Our results are discussed in the light of clinical experience of allogeneic T-cell transfer in scid infants.