Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative campath-1H exposure

J. M. Mathew, W. DeFaria, T. Kato, Bonnie B Blomberg, M. Carreno, Sergio F Santiago, D. Weppler, V. Esquenazi, J. Miller, A. G. Tzakis

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Abstract

A number of recent reports in clinical and experimental intestinal transplantation have suggested that the donor lymphocytes present in and around the gastrointestinal system are potent mediators of graft-versus-host (GvH) reactivity and that GvH responses may contribute to posttransplant morbidity. Therefore, we have tested the proliferative and cytotoxic capabilities of gut-associated lymphocytes from cadaveric donors obtained prerevascularization (pre-r) and about 6 hours postrevascularization (post-r) in recipients pretreated with Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the recipient and third-party alloantigenic stimulating cells. However, similar preparations from the post-r samples responded in MLR at significantly lower levels (P <. 01). This post-r decrease in responsiveness was not observed in similar lymphocyte samples obtained from donors of recipients not treated with Campath-1H. Both the pre-r and post-r samples had similar flow cytometric profiles, suggesting that there was no receptor loss in these lymphoid tissues by the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely, in preliminary experiments where the donor were treated with Campath-1H, it was observed that very few lymphocytes could be obtained from intestinal tissues (n = 3). These results suggested that Campath-1H treatment of the recipient could bring about a drastic reduction in an otherwise strong GvH reactivity by the donor intestinal immune cells.

Original languageEnglish
Pages (from-to)1375-1378
Number of pages4
JournalTransplantation Proceedings
Volume37
Issue number2
DOIs
StatePublished - Mar 1 2005

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Lymphocytes
Mixed Lymphocyte Culture Test
Transplants
Lymphoid Tissue
Intestinal Mucosa
alemtuzumab
Mucous Membrane
Transplantation
Lymph Nodes
Morbidity
Antibodies

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative campath-1H exposure. / Mathew, J. M.; DeFaria, W.; Kato, T.; Blomberg, Bonnie B; Carreno, M.; Santiago, Sergio F; Weppler, D.; Esquenazi, V.; Miller, J.; Tzakis, A. G.

In: Transplantation Proceedings, Vol. 37, No. 2, 01.03.2005, p. 1375-1378.

Research output: Contribution to journalArticle

Mathew, J. M. ; DeFaria, W. ; Kato, T. ; Blomberg, Bonnie B ; Carreno, M. ; Santiago, Sergio F ; Weppler, D. ; Esquenazi, V. ; Miller, J. ; Tzakis, A. G. / Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative campath-1H exposure. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 2. pp. 1375-1378.
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