Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent----F1 chimeras that are selectively tolerant of host alloantigens.
Treatment of murine lymphocytes with 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-2b phenotype. Whereas B6----B6D2F1 spleen cells demonstrated alloproliferative and allocytotoxic responses toward H-2k bearing spleen cells, no H-2d specific proliferative or cytotoxic responses could be elicited. B6----B6D2F1 spleen cells did not suppress the generation of anti-H-2d or anti-H-2k proliferative or cytotoxic responses from control B6 spleen cells. Furthermore, addition of rat concanavalin A supernatants did not reconstitute anti-H-2d 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.
Thiele
D L
DL
Department of Internal Medicine, University of Texas Health Science Center, Southwestern Medical School, Dallas 75235.
Calomeni
J A
JA
Lipsky
P E
PE
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D003433:Crosses, Genetic; D004151:Dipeptides / Q000494:pharmacology*; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D007121:Immunocompetence / Q000187:drug effects*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D011828:Radiation Chimera; D013154:Spleen / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004151:Dipeptides; D006183:H-2 Antigens; C045139:leucyl-leucine-methyl ester