Modulatory effects of human donor bone marrow cells on allogeneic cellular immune responses

James M. Mathew, Manuel Carreno, Laphalle Fuller, Camillo Ricordi, Andreas Tzakis, Violet Esquenazi, Joshua Miller

Research output: Contribution to journalArticle

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Abstract

Background. In order to evaluate whether immuno-regulatory mechanisms are brought about by human donor bone marrow cell infusions accompanying organ transplantation, we established in vitro culture systems analogous to the transplant model. Methods. Cell-mediated lympholysis (CML) and mixed lymphocyte culture (MLC) responses of peripheral blood lymphocytes or spleen cells stimulated with irradiated cadaver donor spleen cells in the presence of specific donor vertebral-body bone marrow cell (DBMC) modulators were tested. Results. When compared with spleen cells as modulator controls, DBMC inhibited both the proliferative and cytotoxic responses in a dose-dependent manner. Use of unirradiated and T cell-depleted DBMC was required for detection of the inhibitory activity. Furthermore, DBMC had to be added within the first 2 days after the initiation of the cultures for the down- regulation of CML (MLC) to occur. The down-regulation of MLC responses could not be shown to be antigen (donor) specific. Physical separation of DBMC from the responder-stimulator cells using the trans-well system abrogated modulation of the CML (and MLC) reactions, suggesting the requirement of cell-cell contact for modulatory effect. The inhibitory activity by DBMC could not be overcome by addition of up to 200 U/ml of exogenous recombinant interleukin 2 to the cultures. However, it could be abrogated by restimulation with donor spleen cells, indicating that donor reactive cells were not deleted by DBMC in short-term cultures. Conclusions. These results showed a regulatory role for DBMC in cellular immune responses against donor cell alloantigens, supporting the rationale for DBMC for facilitating clinical allograft acceptance.

Original languageEnglish
Pages (from-to)686-692
Number of pages7
JournalTransplantation
Volume63
Issue number5
DOIs
StatePublished - Mar 15 1997

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Cellular Immunity
Bone Marrow Cells
Spleen
Lymphocytes
Down-Regulation
Mixed Lymphocyte Culture Test
Isoantigens
Organ Transplantation
Cadaver
Interleukin-2
Allografts
T-Lymphocytes
Transplants
Antigens

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Modulatory effects of human donor bone marrow cells on allogeneic cellular immune responses. / Mathew, James M.; Carreno, Manuel; Fuller, Laphalle; Ricordi, Camillo; Tzakis, Andreas; Esquenazi, Violet; Miller, Joshua.

In: Transplantation, Vol. 63, No. 5, 15.03.1997, p. 686-692.

Research output: Contribution to journalArticle

Mathew, JM, Carreno, M, Fuller, L, Ricordi, C, Tzakis, A, Esquenazi, V & Miller, J 1997, 'Modulatory effects of human donor bone marrow cells on allogeneic cellular immune responses', Transplantation, vol. 63, no. 5, pp. 686-692. https://doi.org/10.1097/00007890-199703150-00013
Mathew, James M. ; Carreno, Manuel ; Fuller, Laphalle ; Ricordi, Camillo ; Tzakis, Andreas ; Esquenazi, Violet ; Miller, Joshua. / Modulatory effects of human donor bone marrow cells on allogeneic cellular immune responses. In: Transplantation. 1997 ; Vol. 63, No. 5. pp. 686-692.
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