Mechanisms of suppression in mixed allogeneic chimeras
Cells with the ability to suppress cytotoxic T lymphocyte generation are found in the spleens of whole-body-irradiated (WBI) mixed allogeneic and syngeneic bone marrow transplant recipients in the early weeks after BMT. Previous studies have indicated that suppression is mediated by null cells similar to natural suppressor (NS) cells (1), and have ruled out several possible trivial explanations for the suppressive effect. We report here the results of additional experiments designed to assess possible mechanisms of suppression. We compared the cell populations after 5 days' incubation of cultures containing normal responding splenocytes plus irradiated allogeneic stimulator cells, with or without a cocultured suppressive chimeric splenocyte population. The data indicate that total viable cell yields are only slightly reduced, if at all, in suppressed cultures, but that the proportion of T cells is markedly reduced as measured at the end of the incubation period. Splenocytes from early BMT recipients do not appear to proliferate during the suppression of a mixed lymphocyte culture, and such populations represent only 15% of cells at the end of the 5-day incubation period. Suppression is strongest when the suppressive population is added at the initiation of MLC, and is lost if addition is delayed beyond day 3. Suppression can be overcome by T cell growth factor (TCGF)--and, to a lesser extent, by recombinant IL-2 (rIL-2), although resting suppressive populations do not consume appreciable amounts of these lymphokines. These results therefore suggest that suppression in MLC may occur primarily during the induction of helper T lymphocytes.
- Research Organization:
- National Cancer Institute, Bethesda, MD (USA)
- OSTI ID:
- 7037199
- Journal Information:
- Transplantation; (United States), Vol. 46
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW
TRANSPLANTS
IMMUNITY
RADIOINDUCTION
LYMPHOCYTES
CELL PROLIFERATION
CELL CULTURES
GROWTH FACTORS
IMMUNOSUPPRESSION
LYMPHOKINES
MICE
RADIATION CHIMERAS
SPLEEN CELLS
WHOLE-BODY IRRADIATION
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
IRRADIATION
LEUKOCYTES
MAMMALS
MATERIALS
MITOGENS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals