Induction of specific transplantation immunity by oral immunization with allogeneic cells

Abstract

SUMMARYOral administration of antigen has been shown to be effective for both positive and negative modulation of immune responses. In the present study we characterized changes in the reactivity of the immune system after oral immunization with allogeneic spleen cells. Mice were orally immunized for 10 consecutive days with fresh allogeneic spleen cells, and the phenotype, proliferative response, cytotoxic activity and cytokine production pro®le of recipient spleen cells were assessed 1 or 7 days after the last immunization dose. Although no signi®cant changes in the proportion of CD4 + , CD8 + or CD25 + cells were observed in the spleen of orally immunized mice, signi®cant activation of alloreactivity in spleen cells was found. Cells from orally immunized mice exhibited enhanced proliferation and cytotoxic activity after stimulation with speci®c allogeneic cells in vitro, and produced considerably higher concentrations of interferon-c (IFN-c) and signi®cantly less interleukin (IL)-4 than did cells from control mice. The production of IL-2 was essentially unchanged and that of IL-10 was only slightly increased. The systemic allosensitization induced by oral immunization was demonstrated in vivo by increased resistance to the growth of allogeneic tumours induced by subcutaneous inoculation of high doses of tumour cells. In addition, orthotopic corneal allografts in orally immunized recipients were rejected more rapidly (in a secondset manner) than in control, untreated recipients. These data show that oral immunization with allogeneic cells modulates individual components of the immune response and that speci®c transplantation immunity, rather than tolerance, is induced in the treated recipients.

Role of Cytokines in Allograft Rejection

“…Other groups have similarly established this relationship between Th1/Th2 cytokine production and corneal allograft survival [82]. A most interesting study recently examined the incidence of a variety of inflammatory cytokines in aqueous humour in relation to corneal disease and subsequent corneal graft survival or rejection [83].…”

Inducción de tolerancia por vía oral en trasplante de órganos y tejidos. Revisión de la Literatura

“…18 Likewise, studies in mice have shown how the intake of CD4 lymphocytes from the donor decreases the induction of pro-inflammatory cascades and increases IL-10 levels in cases of spleen transplantation. 19,[65][66][67] Finally, combined therapy of CD4 lymphocytes and anti-CD3 orally demonstrated promising results in kidney and heart transplantation in murine models by prolonging the survival of the grafts by more than 100 days. 68,69,71 None of the interventions described above have been studied in humans, so despite having a physiological basis, these results cannot be extrapolated or presumed to be safe in a human context.…”