Graft-versus-host disease and graft-versus-leukemia effect in mice grafted with peripheral newborn blood.
We previously used peripheral newborn blood (NBB) as a possible in vivo experimental model for cord blood (CB) transplantation and showed that B10.D2 NBB cells successfully reconstituted adult (DBA/2 x B10.D2)F1 mice without causing graft-versus-host disease (GVHD), probably because of their phenotypic and functional immaturity. Here we investigated the influence of T-cell maturation occurring in NBB cells during the early postbirth period on the degree of engraftment, the incidence of GVHD, and the graft-versus-leukemia (GVL) potential. These parameters were compared in recipients grafted with bone marrow (BM) cells. We observed an increased percentage of CD4(+) mature T cells accompanied by the acquisition of proliferative responses to phytohemagglutinin (PHA) and to allogeneic cells of day-5 NBB cells. The capacity of day-2 NBB to engraft was moderately reduced and recipients developing GVHD were occasionally observed after the graft of day-5 NBB cells. No GVL effect was evidenced regardless of the time of postbirth blood collection. However, the GVL effect can be obtained by the delayed infusion of donor mature T cells to recipients grafted with day-0 NBB, without causing GVHD. In contrast, the same protocol applied to mice grafted with BM cells induced GVHD mortality of all recipients. Interleukin (IL)-10 but not IL-2 messenger RNA was expressed in NBB cells as opposed to BM cells. These findings suggest that, in terms of GVHD incidence, delayed infusion of mature T cells as post-transplant tumor immunotherapy would be more effective when applied after CB than after BM transplantation.
de La Selle
V
V
INSERM Unité 267, Immunogénétique des Allogreffes, Villejuif, France.
Gluckman
E
E
Bruley-Rosset
M
M
D000818:Animals; D000831:Animals, Newborn / Q000097:blood*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003208:Concanavalin A / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000096:biosynthesis; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000637:transplantation
D007376:Interleukin-2; D012333:RNA, Messenger; D003208:Concanavalin A; D016753:Interleukin-10