Striking augmentation of hematopoietic cell chimerism in noncytoablated allogeneic bone marrow recipients by flt3 ligand and tacrolimus

The influence of granulocyte-macrophage colony-stimulating factor (GM- CSF) and the recently identified hematopoietic stem-progenitor cell mobilizing factor flt3 ligand (FL) on donor leukocyte microchimerism in noncytodepleted recipients of allogeneic bone marrow (BM) was compared. B10 mice (H2b) given 50 x 106 allogeneic (B10.BR [H2(k)]) BM cells also received either GM-CSF (4 μg/day s.c.), FL (10 μg/day i.p.), or no cytokine, with or without concomitant tacrolimus (formerly FK506; 2 mg/kg) from day 0. Chimerism was quantitated in the spleen 7 days after transplantation by both polymerase chain reaction (donor DNA [major histocompatibility complex class II; I-E(k)]) and immunohistochemical (donor [I-E(k+)] cell) analyses. Whereas GM-CSF alone significantly augmented (fivefold) the level of donor DNA in recipients' spleens, FL alone caused a significant (60%) reduction. Donor DNA was increased 10-fold by tacrolimus alone, whereas coadministration of GM-CSF and tacrolimus resulted in a greater than additive effect (28-fold increase). A much more striking effect was observed with FL + tacrolimus (>125-fold increase in donor DNA compared with BM alone). These findings were reflected in the relative numbers of donor major histocompatibility complex class II+ cells (many resembling dendritic cells) detected in spleens, although quantitative differences among the groups were less pronounced. Evaluation of cytotoxic T lymphocyte generation by BM recipients' spleen cells revealed that FL alone augmented antidonor immunity and that this was reversed by tacrolimus. Thus, although FL may potentiate antidonor reactivity in nonimmunosuppressed, allogeneic BM recipients, it exhibits potent chimerism-enhancing activity when coadministered with recipient immunosuppressive therapy. This property of FL may offer considerable potential for the augmentation of microchimerism, with therapeutic implications for organ allograft survival and tolerance induction

A novel approach to nano topology via neutrosophic sets

The main objective of this study is to introduce a new hybrid intelligent structure called Neutrosophic nano topology. Fuzzy nano topology and intuitionistic nano topology can also be deduced from the neutrosophic nano topology. Based on the neutrosophic nano approximations we have classified neutrosophic nano topology. Some properties like neutrosophic nano interior and neutrosophic nano closure are derived

Flt-3 Ligand Increases Microchimerism But Can Prevent the Therapeutic Effect of Donor Bone Marrow in Transiently Immunosuppressed Cardiac Allograft Recipients

C3H (H2(k)) mice received 50 x 10(6) B10 (H2(b)) bone marrow (BM) cells either alone or with fit-3 ligand (FL) (10 mu g/day), tacrolimus (2 mg/kg/day), or both agents for 7 days, Donor MHC class II+ (IA(b+)) cells were quantitated in spleens by immunohistochemical analysis, and donor class II DNA detected in BM by PCR, Donor cells were rare in the BM alone and BM + FL groups, whereas there was a substantial increase in chimerism in the BM + tacrolimus group, Addition of FL to BM + tacrolimus led to a further eightfold increase in donor cells and enhanced donor DNA compared with the BM + tacrolimus group, This increase in donor cells was almost 500-fold compared with BM alone, C3H recipients of B10 heart allografts given perioperative B10 BM and tacrolimus (days 0-13) exhibited a markedly extended median graft survival time (MST, 42 days) compared with those given tacrolimus alone (MST, 22 days), Addition of FL (10 mu g/day; 7 days) to BM + tacrolimus prevented the beneficial effect of donor BM (MST, 18 days), BM alone or BM + FL resulted in uniform early heart graft failure (MST < 8 days), Functional studies revealed maximal antidonor MLR and CTL activities in the BM- and BM + FL-treated groups, with minimal activity in the tacrolimus-treated groups, Thus, dramatic growth factor-induced increases in chimerism achieved under cover of immunosuppression may result in augmented antidonor T cell reactivity and reduced graft survival after immunosuppressive drug withdrawal, With FL, this map reflect striking augmentation of immunostimulatory dendritic cells