Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H‐2 class II mismatch. Different mechanisms operate in tolerization across an H‐2 class I vs. H‐2 class II disparity

Abstract

Previously, we have shown that the intravenous (i.v.) injection of allogeneic lymphocytes across an H-2 class I-mutant disparity leads to specific skin allograft tolerance caused by irradiation-sensitive donor T cells, which function as veto cells. In the present study, we show that the i.v. injection of H-2 class II-incompatible spleen cells also results in specific skin allograft tolerance. However, tolerance induction depends on the presence of irradiation-resistant non-T cells in the donor cell inoculum. Thus, different mechanisms operate in tolerance induction across an H-2 class I vs. H-2 class II mismatch. I.v. injection of allogeneic spleen cells across an H-2 class I plus class II disparity does not result in skin allograft tolerance. Finally, our data show that transfusion-induced suppression of the delayed-type hypersensitivity response against alloantigens does not correlate with skin allograft tolerance induced by i.v. injected allogeneic lymphocytes. In conclusion, the type of H-2 mismatch between transfusion donor and recipient not only determines the occurrence of allograft tolerance but also the mechanism leading to tolerization.

Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand.

“…They may also be more effective than naive T cells in inducing costimulatory activity and converting transfused lymphocytes into immunogenic APCs. Others have reported tolerance induction across MHC barriers by injecting spleen cells without removing nonlymphoid APCs (32,46), but we find this possible only if CD40L/CD40 interaction is blocked. …”

Induction of Immunologic Tolerance for Transplantation

“…The protocol for intrathymic injection of alloantigen required in the DST for tolerance induction to MHC class II antigens (426).…”

“…Strategies for overcoming hyperacute rejection include genetic engineering of xenograft donors to express ''Natural antibodies'' in human recipients cause hyp-human complement inhibitors like CD46, CD55, and CD59 eracute rejection of ''discordant'' vascularized xenografts (67,280,338) or to knock out genes required for the ex- (67,109,328,426). These predominantly IgM antibodies pression of a-galactosyl residues (228,441).…”

Donor-lymphocyte infusion induces transplantation tolerance by activating systemic and graft-infiltrating double-negative regulatory T cells

“…There are many experimental models in which tolerance can be induced by donor-lymphocyte infusion (DLI) before transplantation, [1][2][3][4][5][6][7] and the effects of DLI have also been observed clinically in recipients of renal, cardiac, and bone marrow transplants. [8][9][10][11][12][13][14] Several mechanisms have been postulated to explain DLI-induced tolerance, including mixed allogeneic chimerism, [15][16][17][18] deletion of donor-reactive T cells, [19][20][21][22][23] induction of clonal anergy, 24 immune deviation, [24][25][26] and regulatory T cells.…”