Inhibition of alloantigen-primed memory CD4+ and CD8+ T cells by hematopoietic chimerism in mice.
Donor-reactive memory T cells present a special hurdle in transplantation. Although hematopoietic chimerism is effective for inducing donor-specific tolerance, the effects on memory T cells are unclear. Here, we induced stable chimerism and tolerance in mice (Tolerance group, n = 6) by donor-specific transfusion (DST) plus anti-CD154 monoclonal antibody (mAb), avoiding the toxic myeloablative conditioning treatment to assist bone marrow transplantation (DST/aCD154&BMTx). We then transferred memory CD4(+) or CD8(+) T cells from donor antigen primed mice to the tolerance-induced recipients 4 days after heart transplantation (Tol/CD4(+) Tm group and Tol/CD8(+) Tm group, n = 6, respectively), but neither of these memory T-cell subsets had an effect on the permanent graft survival (median survival time > 100 days). The unaltered rate of memory T cells in spleen and anergy to donor antigen in vitro demonstrated that these memory T cells were well controlled. The chimerism-promoting protocol DST/aCD154&BMTx produced an immune environment that included high levels of regulatory T cells (Tregs), microchimerism and TGF-beta, all of which may act in suppressing the donor-reactive memory CD4(+) or CD8(+) T cells. These findings have potentially important implications for designing approaches to suppressing memory T cells for success of transplantation.
Lan
T
T
Organ Transplantation Institute of Xiamen University, Xiamen City, Fujian Province, China.
Chen
J
J
Xia
J
J
Wang
Y
Y
Xie
B
B
Wang
F
F
Qi
Z
Z
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000737:chemistry / Q000235:genetics; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics; D007519:Isoantigens / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D018183:Transplantation Chimera
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D007519:Isoantigens; D012313:RNA; D007371:Interferon-gamma