Cardiac allograft survival across major histocompatibility complex barriers in the rhesus monkey following T lymphocyte-depleted autologous marrow transplantation. IV. Immune reconstitution.
Studies of postmyeloablative immune reconstitution have been reported for allogeneic bone marrow transplantation and also for non-T cell-depleted autologous/syngeneic BMT. However, there is a paucity of information regarding immune recovery following T cell-depleted autologous/syngeneic BMT. We have developed a primate transplantation tolerance model in which rhesus monkeys were conditioned with total-body irradiation and extensively T cell-depleted autologous BMT and given a major histocompatibility complex-mismatched heterotopic cardiac allograft. This model provided an opportunity to study peripheral immune recovery following T cell-depleted autologous BMT. Limiting dilution analysis was used to quantify marrow T cells following depletion (2.8% to 25.6% marrow T cells predepletion, 0.00014% to 0.036% residual marrow T cells postdepletion). We found that (1) hematopoietic engraftment was prompt despite extensive marrow T cell depletion, (2) reconstitution of CD4+ helper T cells and CD8+ cytotoxic T cells were substantially delayed (6-12 months) compared with the recovery of CD8+ suppressor T cells, CD16+ NK cells, and CD20+ B cells, (3) distinction between CD8+ cytotoxic T cells and CD8+ suppressor T cells by the CD28 marker was critical in revealing the markedly discrepant recoveries of those subsets, and (4) immune reconstitution resembled that observed in recipients of T cell-depleted allogeneic and non-T cell-depleted autologous/syngeneic BMT, suggesting that the pattern of immune recovery following BMT is not substantially influenced by either allogeneic effects or the number of transferred T cells over a range of values.
Moses
R D
RD
Experimental Immunology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892.
Sharrow
S O
SO
Stephany
D A
DA
Orr
K S
KS
Gress
R E
RE
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006410:Hematopoiesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008253:Macaca mulatta; D008285:Major Histocompatibility Complex; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014916:Whole-Body Irradiation
D000943:Antigens, Differentiation