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Chimerism and tolerance in rat recipients of intestinal allografts from ALS-treated donors with and without adjunct naïve-donor-strain bone-marrow cells.
Transplantation. 2003 May 15; 75(9):1575-81.T

Abstract

BACKGROUND

BN --> LEW small-intestine transplantation (SITx) given a 28-day course of tacrolimus results in partial tolerance and prolonged alloengraftment despite the development of indolent chronic rejection (CR). We determined whether the CR was associated with the quantity or quality of passenger leukocytes contained in the unmodified or antilymphocyte serum (ALS)-depleted BN intestine at the time of transplantation, and with the subsequent migration and persistence of these donor leukocytes in the LEW recipients (chimerism).

METHODS

Four experimental cohorts were defined by differences of the BN allografts and by the infusion (or not) of naïve donor (bone marrow cells [BMC]) on the day of the BN --> LEW SITx. All LEW recipients were treated with the same 28-day course of tacrolimus. The LEW animals received: (1) unaltered intestine; (2) intestine from ALS-treated donor; (3) intestine from ALS-treated donor plus BMC from naive BN donor on day 0; and (4) unaltered intestine and BMC from unmodified (naïve) BN donor.

RESULTS

Blood chimerism during the first 2 weeks after transplantation was lowest in the recipients of intestine from ALS-treated donors (groups 2 and 3), apparently because of the nearly complete elimination from the bowel of alphabetaTCR+ passenger leukocytes. After 2 weeks posttransplant to 5 months, greater than 2% of circulating donor cells were seen in animals given adjunct BMC from naïve BN donors (groups 3 and 4); this was associated with the absence of CR in the intestinal allografts. With lower levels of chimerism, moderate CR including arteritis and fibrosis in the Peyer's patches and mesenteric lymph nodes was found in the intestinal grafts of all group 1 and group 2 animals. Nevertheless, the CR-prone recipients in groups 1 and 2 had equivalent weight gain for greater than or equal to 150 days as in the CR-free groups 3 and 4. Detailed tissue chimerism studies in groups 1 to 3 showed that most of the donor cells in the gut-associated lymphoid tissues were rapidly replaced, but that the residual donor constituency of up to 6% in the allografts of group 3 was nearly 10-fold greater at 150 days than in groups 1 and 2 and closely reflected the findings in blood.

CONCLUSION

The development of CR in intestinal allografts to which the recipients are partially tolerant is associated with a decline with time of donor-leukocyte chimerism. Multilineage chimerism in the recipient, and a similar profile of donor cells in the allografts, is better achieved with infused donor BMC than with the normal intestinal passenger leukocytes of the intestine. The difference may be because of a higher number of precursor and pluripotent stem cells in BMC.

Authors+Show Affiliations

Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12792518

Citation

Nakao, Atsunori, et al. "Chimerism and Tolerance in Rat Recipients of Intestinal Allografts From ALS-treated Donors With and Without Adjunct Naïve-donor-strain Bone-marrow Cells." Transplantation, vol. 75, no. 9, 2003, pp. 1575-81.
Nakao A, Nalesnik MA, Ishikawa T, et al. Chimerism and tolerance in rat recipients of intestinal allografts from ALS-treated donors with and without adjunct naïve-donor-strain bone-marrow cells. Transplantation. 2003;75(9):1575-81.
Nakao, A., Nalesnik, M. A., Ishikawa, T., Azhipa, O., Demetris, A. J., & Murase, N. (2003). Chimerism and tolerance in rat recipients of intestinal allografts from ALS-treated donors with and without adjunct naïve-donor-strain bone-marrow cells. Transplantation, 75(9), 1575-81.
Nakao A, et al. Chimerism and Tolerance in Rat Recipients of Intestinal Allografts From ALS-treated Donors With and Without Adjunct Naïve-donor-strain Bone-marrow Cells. Transplantation. 2003 May 15;75(9):1575-81. PubMed PMID: 12792518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chimerism and tolerance in rat recipients of intestinal allografts from ALS-treated donors with and without adjunct naïve-donor-strain bone-marrow cells. AU - Nakao,Atsunori, AU - Nalesnik,Michael A, AU - Ishikawa,Takashi, AU - Azhipa,Olga, AU - Demetris,Anthony J, AU - Murase,Noriko, PY - 2003/6/7/pubmed PY - 2003/6/20/medline PY - 2003/6/7/entrez SP - 1575 EP - 81 JF - Transplantation JO - Transplantation VL - 75 IS - 9 N2 - BACKGROUND: BN --> LEW small-intestine transplantation (SITx) given a 28-day course of tacrolimus results in partial tolerance and prolonged alloengraftment despite the development of indolent chronic rejection (CR). We determined whether the CR was associated with the quantity or quality of passenger leukocytes contained in the unmodified or antilymphocyte serum (ALS)-depleted BN intestine at the time of transplantation, and with the subsequent migration and persistence of these donor leukocytes in the LEW recipients (chimerism). METHODS: Four experimental cohorts were defined by differences of the BN allografts and by the infusion (or not) of naïve donor (bone marrow cells [BMC]) on the day of the BN --> LEW SITx. All LEW recipients were treated with the same 28-day course of tacrolimus. The LEW animals received: (1) unaltered intestine; (2) intestine from ALS-treated donor; (3) intestine from ALS-treated donor plus BMC from naive BN donor on day 0; and (4) unaltered intestine and BMC from unmodified (naïve) BN donor. RESULTS: Blood chimerism during the first 2 weeks after transplantation was lowest in the recipients of intestine from ALS-treated donors (groups 2 and 3), apparently because of the nearly complete elimination from the bowel of alphabetaTCR+ passenger leukocytes. After 2 weeks posttransplant to 5 months, greater than 2% of circulating donor cells were seen in animals given adjunct BMC from naïve BN donors (groups 3 and 4); this was associated with the absence of CR in the intestinal allografts. With lower levels of chimerism, moderate CR including arteritis and fibrosis in the Peyer's patches and mesenteric lymph nodes was found in the intestinal grafts of all group 1 and group 2 animals. Nevertheless, the CR-prone recipients in groups 1 and 2 had equivalent weight gain for greater than or equal to 150 days as in the CR-free groups 3 and 4. Detailed tissue chimerism studies in groups 1 to 3 showed that most of the donor cells in the gut-associated lymphoid tissues were rapidly replaced, but that the residual donor constituency of up to 6% in the allografts of group 3 was nearly 10-fold greater at 150 days than in groups 1 and 2 and closely reflected the findings in blood. CONCLUSION: The development of CR in intestinal allografts to which the recipients are partially tolerant is associated with a decline with time of donor-leukocyte chimerism. Multilineage chimerism in the recipient, and a similar profile of donor cells in the allografts, is better achieved with infused donor BMC than with the normal intestinal passenger leukocytes of the intestine. The difference may be because of a higher number of precursor and pluripotent stem cells in BMC. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/12792518/Chimerism_and_tolerance_in_rat_recipients_of_intestinal_allografts_from_ALS_treated_donors_with_and_without_adjunct_naïve_donor_strain_bone_marrow_cells_ L2 - https://doi.org/10.1097/01.TP.0000061225.81051.06 DB - PRIME DP - Unbound Medicine ER -