BIOMAT Database Logo BIOMAT Database Logo

Fractionated dosing of cyclophosphamide for establishing long-lasting skin allograft survival, stable mixed chimerism, and intrathymic clonal deletion in mice primed with allogeneic spleen cells. 1997

Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

BACKGROUND Injection of allo-spleen cells (SC) followed by a single dose of cyclophosphamide (CP) can induce tolerance of tumor and/or skin allografts in mice. To minimize the damage caused by CP, fractionation of CP that can establish long-lasting skin graft survival, stable mixed chimerism, and intrathymic clonal deletion in the host was investigated in the present study. METHODS Allo-SC (10(8)) were given intravenously on day 0. CP at 200 mg/kg was given intraperitoneally on day 2 in a single dose (CP 200x1 group). CP at 100, 66, 50, 40, and 33 mg/kg was given daily from day 1 through days 2, 3, 4, 5 and 6, respectively, in the fractionated doses (CP 100x2, 66x3, 50x4, 40x5, and 33x6 groups; total dose=200 mg/kg). Allografting was performed on day 14. RESULTS In a fully allogeneic combination of C57BL/6 (H2b)-->AKR (H2k, Mls-1a), an EL-4 tumor (H2b) was specifically accepted to kill the AKR mice in all of the SC+CP 200x1, 100x2, 66x3, 50x4, 40x5, and 33x6 groups (n=6), but C57BL/6 skin graft survival was not prolonged in any of the tumor-tolerant groups. In an H2-identical combination of AKR-->C3H (H2k, Mls-1b), AKR skin graft survival was prolonged remarkably (80-90 days) in the SC+CP 200x1, 100x2, and 66x3 groups (n=5-11), but was prolonged moderately (20-60 days) in the SC+CP 50x4 and 40x5 groups. In both of the SC+CP 200x1 and 66x3 groups in the AKR-->C3H combination, mixed chimerism was maintained for as long as 100 days after tolerance induction in both the spleen and thymus, associated with intrathymic clonal deletion of Vbeta6+ T cells. The decreases in leukocyte count, hemoglobin level, spleen weight, SC count, and body weight were significantly smaller in the SC+CP 66x3 group than in the SC+CP 200x1 group. CONCLUSIONS Fractionated CP is effective in ameliorating the compromised state induced by a single dose of CP. To induce a long-lasting skin allograft survival associated with stable mixed chimerism and intrathymic clonal deletion in an H2-identical combination, 200 mg/kg of CP can be divided into three or fewer fractions.

UI MeSH Term Description Entries
D007970 Leukopenia A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000). Leukocytopenia,Leukocytopenias,Leukopenias
D008806 Mice, Inbred AKR An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. Mice, AKR,Mouse, AKR,Mouse, Inbred AKR,AKR Mice,AKR Mice, Inbred,AKR Mouse,AKR Mouse, Inbred,Inbred AKR Mice,Inbred AKR Mouse
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260 Female Females
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft

Related Publications

Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
The requirement of intrathymic mixed chimerism and clonal deletion for a long-lasting skin allograft tolerance in cyclophosphamide-induced tolerance.
September 1990, European journal of immunology,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Induction of permanent mixed chimerism and skin allograft tolerance across fully MHC-mismatched barriers by the additional myelosuppressive treatments in mice primed with allogeneic spleen cells followed by cyclophosphamide.
July 2000, Journal of immunology (Baltimore, Md. : 1950),
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Importance of intrathymic mixed chimerism for the maintenance of skin allograft tolerance across fully allogeneic antigens in mice.
March 1999, Immunology,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Sequential mechanisms of cyclophosphamide-induced skin allograft tolerance including the intrathymic clonal deletion followed by late breakdown of the clonal deletion.
September 1990, Journal of immunology (Baltimore, Md. : 1950),
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.
September 2000, Transplantation,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Targeting apoptosis to induce stable mixed hematopoietic chimerism and long-term allograft survival without myelosuppressive conditioning in mice.
August 2013, Blood,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Importance of intrathymic mixed chimerism for maintenance of skin allograft tolerance across fully allogeneic (entire major H-2 plus multiminor histocompatibility) antigen barriers in mice.
April 1994, Transplantation proceedings,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Intrathymic and extrathymic clonal deletion of T cells.
April 1995, Current opinion in immunology,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys.
January 1995, Transplantation,
Q W Zhang, and H Mayumi, and M Umesue, and Y Tomita, and K Nomoto, and H Yasui
The necessity of both allogeneic antigens and stem cells for cyclophosphamide-induced skin allograft tolerance in mice.
February 1989, Immunobiology,
Copied contents to your clipboard!