Haploidentical donor T cells fail to facilitate engraftment but lessen the immune response of host T in murine fetal transplantation

Jeng Chang Chen, Ming-Ling Chang, Hanmin Lee, Marcus O. Muench*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

The effects of donor T cells, or their CD8+ subset, on engraftment and tolerance induction in fetal transplantation were evaluated using an F1-into-parent mouse-model that does not permit a graft-versus-host effect. Gestational day 13 C57BL/6 (H-2Kb) fetuses were transplanted with B6D2F1 (H-2Kb/d) light density bone marrow cells (LDBMC) containing 1-2% T cells, T-cell depleted bone marrow cells (TDBMC, <0.1% T cells), or TDBMC with enriched CD8+ T cells (CD8). Chimaerism levels in the peripheral blood, spleen and bone marrow were usually below 0.2% in all groups, indicating that T cells do not improve engraftment without a graft-versus-host effect. A significant, but transient, wave of donor cells was seen in the peripheral blood at 1 month of age in the CD8 and LDBMC groups. Relatively high levels of chimaerism (<17%) were sometimes detected in the peritoneal cavities of recipients. T-cell tolerance specific to donor cells was evaluated in mixed lymphocyte cultures. The CD8 and LDBMC groups had significantly lower T-cell responses than untransplanted controls. These findings indicate that in utero transplantation of haploidentical donor CD8+ or CD3+ cells can help to lessen the immune response of host T cells towards donor cells. The persistence of donor cells in the peritoneal cavity also correlated with tolerance induction.

Original languageEnglish
Pages (from-to)377-384
Number of pages8
JournalBritish Journal of Haematology
Volume126
Issue number3
DOIs
StatePublished - 08 2004

Keywords

  • CD8
  • Engraftment
  • Fetus
  • T cells
  • Tolerance induction

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