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Loss of marrow allograft resistance in mice with transplanted methylcholanthrene-induced sarcomas
Abstract:
To determine if the effector cells responsible for allogeneic marrow stem cell rejections were suppressed in mice with tumors, C57BL/6 (B6) mice were inoculated with 3-methylcholanthrene (MCA)-induced sarcoma cells. When the tumor reached 2.0--2.5 cm in diameter, these mice and control B6 and (BALB/c times A)F1 (CAF1) uninoculated animals were irradiated and given BALB/c marrow cells in the first of a two-step "stem cell rescue" experiment. Four days later, spleen cells of the primary hosts were reinoculated into irradiated CAF1 secondary hosts compatible with BALB/c marrow cells and immunized against B6 antigens. Splenic uptake (percent) of 125I-5-iodo-2'-deoxyuridine 5 days after spleen cell regrafting was used as a measure of cell proliferation and reflected growth of the stem cells in the primary hosts. BALB/c stem cells grew as well in B6 mice with tumors as in CAF1 primary hosts but were rejected by B6 controls. Seeding efficiency of BALB/c stem cells 6 hours after infusion of marrow cells and growth of syngeneic B6 stem cells were enhanced twofold in spleens of tumor-bearing B6 mice. To exclude the possibility that enhanced seeding resulted in greater survival of allogeneic stem cells, more DBA/2 marrow cells were infused into control B6 primary hosts than into tumor-bearing B6 and control DBA/2 mice. Control B6 mice resisted growth of even 7.5 times 10(6) DBA/2 marrow cells, whereas B6 tumor bearers allowed growth of 2.5 times 10(6) cells. No "suppressor cells" capable of inhibiting marrow cell allograft reactions were detected in spleens of tumor-bearing mice. Thus transplanted syngeneic MCA-induced sarcomas abrogated the ability of mice to reject allogeneic marrow stem cells.
Insights
Transplanted tumors in mice abrogated rejection of allogeneic marrow stem cells. Tumor-bearing mice showed enhanced stem cell seeding and growth, unlike control mice, indicating a loss of immune rejection capabilities.
Area of Science:
- Immunology
- Oncology
- Transplantation Biology
Background:
- Allogeneic marrow stem cell transplantation is crucial for treating various diseases.
- The immune system normally rejects foreign (allogeneic) cells, including stem cells.
- Tumor-induced immune suppression is a known phenomenon.
Purpose of the Study:
- To investigate whether tumors suppress the immune cells responsible for rejecting allogeneic marrow stem cells.
- To determine the effect of syngeneic tumors on the host's ability to reject marrow stem cell allografts.
Main Methods:
- Mice with 3-methylcholanthrene-induced sarcomas were used as tumor-bearing models.
- A two-step stem cell rescue experiment involved irradiation and marrow cell infusion.
- Spleen cells were analyzed for their ability to support or reject allogeneic stem cell growth.
- 125I-5-iodo-2 -deoxyuridine uptake measured stem cell proliferation.
Main Results:
- Allogeneic BALB/c stem cells grew in tumor-bearing B6 mice but were rejected by control B6 mice.
- Seeding efficiency and growth of syngeneic B6 stem cells were enhanced in tumor-bearing mice.
- Tumor-bearing mice accepted significantly higher numbers of allogeneic DBA/2 marrow cells compared to controls.
- No suppressor cells were detected in tumor-bearing mice that inhibited allograft reactions.
Conclusions:
- Transplanted syngeneic tumors eliminate the host's capacity to reject allogeneic marrow stem cells.
- Tumor-induced immune modulation, rather than specific suppressor cells, likely underlies this phenomenon.
- This finding has implications for understanding tumor-host interactions and transplantation tolerance.