Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent → F1 chimeras that are selectively tolerant of host alloantigens

Dwain L Thiele, J. A. Calomeni, P. E. Lipsky

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Abstract

Treatment of murine lymphocytes wtih L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 x DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6 → B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6 → B6D2F1 mice were identical with B6 → B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2(b) phenotype. Whereas B6 → B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2(k) bearing spleen cells, no H-2(d) specific proliferative or cytotoxic responses could be elicited. B6 → B6D2F1 spleen cells did not suppress the generation of anti-H-2(d) or anti-H-2(k) proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2(d) responses of B6 → B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent→F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness.

Original languageEnglish (US)
Pages (from-to)2137-2142
Number of pages6
JournalJournal of Immunology
Volume139
Issue number7
StatePublished - 1987

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Isoantigens
Spleen
Natural Killer Cells
Graft vs Host Disease
Bone Marrow Cells
leucylleucine
B-Lymphocytes
Radiation Chimera
leucyl-leucine-methyl ester
T-Lymphocytes
Immunocompetence
Cytotoxic T-Lymphocytes
Concanavalin A
Stem Cells
Bone Marrow
Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent → F1 chimeras that are selectively tolerant of host alloantigens",
abstract = "Treatment of murine lymphocytes wtih L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 x DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6 → B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6 → B6D2F1 mice were identical with B6 → B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2(b) phenotype. Whereas B6 → B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2(k) bearing spleen cells, no H-2(d) specific proliferative or cytotoxic responses could be elicited. B6 → B6D2F1 spleen cells did not suppress the generation of anti-H-2(d) or anti-H-2(k) proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2(d) responses of B6 → B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent→F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness.",
author = "Thiele, {Dwain L} and Calomeni, {J. A.} and Lipsky, {P. E.}",
year = "1987",
language = "English (US)",
volume = "139",
pages = "2137--2142",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
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T1 - Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent → F1 chimeras that are selectively tolerant of host alloantigens

AU - Thiele, Dwain L

AU - Calomeni, J. A.

AU - Lipsky, P. E.

PY - 1987

Y1 - 1987

N2 - Treatment of murine lymphocytes wtih L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 x DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6 → B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6 → B6D2F1 mice were identical with B6 → B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2(b) phenotype. Whereas B6 → B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2(k) bearing spleen cells, no H-2(d) specific proliferative or cytotoxic responses could be elicited. B6 → B6D2F1 spleen cells did not suppress the generation of anti-H-2(d) or anti-H-2(k) proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2(d) responses of B6 → B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent→F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness.

AB - Treatment of murine lymphocytes wtih L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact. The present studies assess the immunocompetence of allogeneic bone marrow chimeras established by reconstituting irradiated (C57BL/6 x DBA/2)F1 (B6D2F1) mice with Leu-Leu-OMe-treated C57BL/6 (B6) bone marrow and spleen cells. Spleen cells from such chimeras were found to have normal B and T cell mitogenic responses. Furthermore, levels of natural-killer cell function were comparable to those observed in B6 → B6 syngeneic radiation chimeras established without Leu-Leu-OMe treatment of donor cells. Spleen cells from B6 → B6D2F1 mice were identical with B6 → B6 or B6 mice in allostimulatory capacity and thus contained no discernible cells of non-H-2(b) phenotype. Whereas B6 → B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2(k) bearing spleen cells, no H-2(d) specific proliferative or cytotoxic responses could be elicited. B6 → B6D2F1 spleen cells did not suppress the generation of anti-H-2(d) or anti-H-2(k) proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2(d) responses of B6 → B6D2F1 chimeric spleen cells. Thus, Leu-Leu-OMe treatment of B6 donor cells not only prevents lethal graft-vs-host disease, but also permits establishment of long-lived parent→F1 chimeras that are selectively tolerant of host H-2 disparate alloantigens, but fully immunocompetent with respect to natural killer cell function, B and T cell mitogenesis, and anti-third party alloresponsiveness.

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