Inhibition of anti-skin allograft immunity induced by infusions with photoin activated effector T lymphocytes — The congenic model

Maritza I. Perez, Carole L. Berger, Yasuhiro Yamane, Lori John, Liliane Laroche, Richard L. Edelson

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We have previously reported the capacity to produce donor-specific tolerance to alloantigens by intravenous exposure to pretreated antidonor T cells. The current study has refined this system by using congenic mice differing only at the H-2 major histocompatibility complex genetic loci. Twelve days after BIO mice received MHC-incompatible B10.D2 skin grafts, their spleno- cytes that included an expanded population of cells mediating rejection were treated with 100 ng/ml 8-meth- oxypsoralen (8-MOP) photoactivated by 1 J/cm2of ultraviolet A prior to infusion into naive B10 recipients. Whereas 8-MOP itself is biologically inert, photoactivated 8-MOP crosslinks DNA by covalently binding to pyrimidine bases. Recipient B10 mice were tested for tolerance to B10.D2 alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), and to in vivo delayed type hypersensitivity assays and challenged with a fresh B10.D2 graft. In vivo, the DTH response of the pretreated B10 mice was specifically suppressed to the relevant alloantigen, correlating with retention of B10.D2 skin grafts for up to 22 days postengraftment without visual evidence of rejection, in comparison to control complete rejection of the skin graft in less than 12 days. In vitro, splenocytes from B10 recipients of pretreated syngeneic splenocytes containing large numbers of B10 anti-B10.D2 T cells proliferated less in MLC and generated lower cytotoxic T cell responses to B10.D2 alloantigens than did controls and suppressed the B10 MLC and CTL responses to B10.D2 alloantigen. These results reveal that, in a highly defined congenic transplantation system, infusions of photoinactivated effector cells resulted in selective inhibition of the in vivo responses that correlated with allograft rejection and permitted prolonged retention of histoincompatible skin grafts. This approach may have significant practical applicability for treatment of human disorders caused by aberrant T cells.

Original languageEnglish
Pages (from-to)1283-1289
Number of pages7
JournalTransplantation
Volume51
Issue number6
DOIs
StatePublished - Jun 1991
Externally publishedYes

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