Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs

Hidetaka Hara, Yih Jyh Lin, Hao Chih Tai, Mohamed Ezzelarab, Mubina A. Quader, Stuart L. Houser, Atsunori Nakao, David K C Cooper

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Mixed chimerism is associated with donor-specific tolerance. Spleen or splenocyte allotransplantation (Tx) is recognized as potentially tolerogenic. There is no definitive report comparing chimerism levels following spleen and splenocyte Tx in a large animal model. We have compared chimerism after spleen, splenocyte, or kidney Tx in pigs. Methods: Outbred (n. =. 5) and MHC-defined miniature (n. =. 1) pigs underwent orthotopic spleen Tx. Outbred pigs received splenocytes through a systemic vein (n. =. 1) or the portal vein (n. =. 3). Kidney Tx (n. =. 2) or concomitant Tx of spleen. +. kidney (n. =. 2) was carried out. All except one recipient pigs were irradiated (700. cGy thymic and 100-125. cGy whole body) on day. -. 2. Cyclosporine or tacrolimus was administered for 42. days. All donors were males and all recipients were females; chimerism in the blood was determined by Quantification-PCR for the donor Y chromosome. Mixed lymphocyte reaction (MLR) was performed before and after Tx. Results: One week after spleen Tx in outbred and MHC-defined pigs, chimerism ranged between 0.8 and 22.5%, and 5.4-20.1%, respectively, and remained between 17.7 and 67.4%, and 2.2-7.4%, respectively, until day 28. One week after splenocyte Tx, chimerism ranged between 0.1 and 8.5%, and decreased to 0.1-0.8% at 3-4. weeks. There was no detectable chimerism 14. days after kidney Tx. The response on MLR of all recipient pigs to donor cells was decreased after Tx, except in one case of splenocyte Tx, indicating that this pig might have become sensitized. After discontinuation of immunosuppression, most isolated spleen or kidney grafts were not rejected, but the kidney was rejected after concomitant spleen. +. kidney Tx. Conclusions: There was a significantly higher level of blood chimerism following spleen Tx compared to splenocyte or kidney Tx. However, concomitant Tx of spleen. +. kidney may be associated with accelerated kidney graft rejection.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalTransplant Immunology
Volume31
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Chimerism
Swine
Spleen
Kidney
Mixed Lymphocyte Culture Test
Y Chromosome
Graft Rejection
Tacrolimus
Portal Vein
Immunosuppression
Cyclosporine
Veins
Animal Models
Transplants
Polymerase Chain Reaction

Keywords

  • Hematopoietic cell chimerism
  • Pig
  • Splenocyte
  • Transplantation, kidney
  • Transplantation, spleen

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation
  • Medicine(all)

Cite this

Hara, H., Lin, Y. J., Tai, H. C., Ezzelarab, M., Quader, M. A., Houser, S. L., ... Cooper, D. K. C. (2014). Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs. Transplant Immunology, 31(3), 125-133. https://doi.org/10.1016/j.trim.2014.09.006

Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs. / Hara, Hidetaka; Lin, Yih Jyh; Tai, Hao Chih; Ezzelarab, Mohamed; Quader, Mubina A.; Houser, Stuart L.; Nakao, Atsunori; Cooper, David K C.

In: Transplant Immunology, Vol. 31, No. 3, 2014, p. 125-133.

Research output: Contribution to journalArticle

Hara, H, Lin, YJ, Tai, HC, Ezzelarab, M, Quader, MA, Houser, SL, Nakao, A & Cooper, DKC 2014, 'Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs', Transplant Immunology, vol. 31, no. 3, pp. 125-133. https://doi.org/10.1016/j.trim.2014.09.006
Hara, Hidetaka ; Lin, Yih Jyh ; Tai, Hao Chih ; Ezzelarab, Mohamed ; Quader, Mubina A. ; Houser, Stuart L. ; Nakao, Atsunori ; Cooper, David K C. / Hematopoietic chimerism following allotransplantation of the spleen, splenocytes or kidney in pigs. In: Transplant Immunology. 2014 ; Vol. 31, No. 3. pp. 125-133.
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abstract = "Background: Mixed chimerism is associated with donor-specific tolerance. Spleen or splenocyte allotransplantation (Tx) is recognized as potentially tolerogenic. There is no definitive report comparing chimerism levels following spleen and splenocyte Tx in a large animal model. We have compared chimerism after spleen, splenocyte, or kidney Tx in pigs. Methods: Outbred (n. =. 5) and MHC-defined miniature (n. =. 1) pigs underwent orthotopic spleen Tx. Outbred pigs received splenocytes through a systemic vein (n. =. 1) or the portal vein (n. =. 3). Kidney Tx (n. =. 2) or concomitant Tx of spleen. +. kidney (n. =. 2) was carried out. All except one recipient pigs were irradiated (700. cGy thymic and 100-125. cGy whole body) on day. -. 2. Cyclosporine or tacrolimus was administered for 42. days. All donors were males and all recipients were females; chimerism in the blood was determined by Quantification-PCR for the donor Y chromosome. Mixed lymphocyte reaction (MLR) was performed before and after Tx. Results: One week after spleen Tx in outbred and MHC-defined pigs, chimerism ranged between 0.8 and 22.5{\%}, and 5.4-20.1{\%}, respectively, and remained between 17.7 and 67.4{\%}, and 2.2-7.4{\%}, respectively, until day 28. One week after splenocyte Tx, chimerism ranged between 0.1 and 8.5{\%}, and decreased to 0.1-0.8{\%} at 3-4. weeks. There was no detectable chimerism 14. days after kidney Tx. The response on MLR of all recipient pigs to donor cells was decreased after Tx, except in one case of splenocyte Tx, indicating that this pig might have become sensitized. After discontinuation of immunosuppression, most isolated spleen or kidney grafts were not rejected, but the kidney was rejected after concomitant spleen. +. kidney Tx. Conclusions: There was a significantly higher level of blood chimerism following spleen Tx compared to splenocyte or kidney Tx. However, concomitant Tx of spleen. +. kidney may be associated with accelerated kidney graft rejection.",
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AU - Hara, Hidetaka

AU - Lin, Yih Jyh

AU - Tai, Hao Chih

AU - Ezzelarab, Mohamed

AU - Quader, Mubina A.

AU - Houser, Stuart L.

AU - Nakao, Atsunori

AU - Cooper, David K C

PY - 2014

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N2 - Background: Mixed chimerism is associated with donor-specific tolerance. Spleen or splenocyte allotransplantation (Tx) is recognized as potentially tolerogenic. There is no definitive report comparing chimerism levels following spleen and splenocyte Tx in a large animal model. We have compared chimerism after spleen, splenocyte, or kidney Tx in pigs. Methods: Outbred (n. =. 5) and MHC-defined miniature (n. =. 1) pigs underwent orthotopic spleen Tx. Outbred pigs received splenocytes through a systemic vein (n. =. 1) or the portal vein (n. =. 3). Kidney Tx (n. =. 2) or concomitant Tx of spleen. +. kidney (n. =. 2) was carried out. All except one recipient pigs were irradiated (700. cGy thymic and 100-125. cGy whole body) on day. -. 2. Cyclosporine or tacrolimus was administered for 42. days. All donors were males and all recipients were females; chimerism in the blood was determined by Quantification-PCR for the donor Y chromosome. Mixed lymphocyte reaction (MLR) was performed before and after Tx. Results: One week after spleen Tx in outbred and MHC-defined pigs, chimerism ranged between 0.8 and 22.5%, and 5.4-20.1%, respectively, and remained between 17.7 and 67.4%, and 2.2-7.4%, respectively, until day 28. One week after splenocyte Tx, chimerism ranged between 0.1 and 8.5%, and decreased to 0.1-0.8% at 3-4. weeks. There was no detectable chimerism 14. days after kidney Tx. The response on MLR of all recipient pigs to donor cells was decreased after Tx, except in one case of splenocyte Tx, indicating that this pig might have become sensitized. After discontinuation of immunosuppression, most isolated spleen or kidney grafts were not rejected, but the kidney was rejected after concomitant spleen. +. kidney Tx. Conclusions: There was a significantly higher level of blood chimerism following spleen Tx compared to splenocyte or kidney Tx. However, concomitant Tx of spleen. +. kidney may be associated with accelerated kidney graft rejection.

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KW - Hematopoietic cell chimerism

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