Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production

Phillip Ruiz, Mehdi Nassiri, Shahik Gregorian, Ana L. Viciana, J. Wayne Streilein

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Abstract

Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult B10.S (H2(s), H2E-) mice that received (B10.SxB10.A)F1 cells at birth and before and following application (and rejection or acceptance) of B10.A (H2(k/d), H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45(hi), PgP-1(hi), Mel-14(neg)) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2K(k)+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but rather is likely more dependent upon clonal deletion processes.

Original languageEnglish
Pages (from-to)1198-1205
Number of pages8
JournalTransplantation
Volume61
Issue number8
DOIs
StatePublished - Apr 27 1996

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Transplantation Tolerance
Eicosanoids
Cytokines
Phenotype
Clonal Deletion
Interleukin-4
Interleukin-2
T-Lymphocytes
Transplants
Skin
Chimerism
Skin Transplantation
Isoantigens
Regulatory T-Lymphocytes
Dinoprostone
Thymus Gland

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production. / Ruiz, Phillip; Nassiri, Mehdi; Gregorian, Shahik; Viciana, Ana L.; Streilein, J. Wayne.

In: Transplantation, Vol. 61, No. 8, 27.04.1996, p. 1198-1205.

Research output: Contribution to journalArticle

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abstract = "Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult B10.S (H2(s), H2E-) mice that received (B10.SxB10.A)F1 cells at birth and before and following application (and rejection or acceptance) of B10.A (H2(k/d), H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45(hi), PgP-1(hi), Mel-14(neg)) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2K(k)+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but rather is likely more dependent upon clonal deletion processes.",
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AU - Ruiz, Phillip

AU - Nassiri, Mehdi

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AU - Viciana, Ana L.

AU - Streilein, J. Wayne

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N2 - Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult B10.S (H2(s), H2E-) mice that received (B10.SxB10.A)F1 cells at birth and before and following application (and rejection or acceptance) of B10.A (H2(k/d), H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45(hi), PgP-1(hi), Mel-14(neg)) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2K(k)+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but rather is likely more dependent upon clonal deletion processes.

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