Effects of T cell depletion in radiation bone marrow chimeras. II. Requirement for allogeneic T cells in the reconstituting bone marrow inoculum for subsequent resistance to breaking of tolerance
The ability of normal recipient-type lymphocytes to break tolerance in long-term allogenic radiation chimeras has been investigated. Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic T cell-depleted (TCD) bone marrow (BM) has previously been shown to lead to mixed chimerism and permanent, specific tolerance to donor and host alloantigen (3-5). If allogeneic T cells are not depleted from the reconstituting inoculum, complete allogeneic chimerism results; however, no clinical evidence for GVHD is observed, presumably due to the protective effect provided by syngeneic TCD BM. This model has now been used to study the effects of allogenic T cells administered in reconstituting BM inocula on stability of long-term tolerance. We have attempted to break tolerance in long-term chimeras originally reconstituted with TCD or non-TCD BM by challenging them with inocula containing normal, nontolerant recipient strain lymphocytes. tolerance was broken with remarkable ease in recipients of mixed marrow inocula in which both original BM components were TCD. In contrast, tolerance in chimeras originally reconstituted with non-TCD allogeneic BM was not affected by such inocula. Susceptibility to loss of chimerism and tolerance was not related to initial levels of chimerism per se, but rather to T cell depletion of allogeneic BM, since chimeras reconstituted with TCD allogeneic BM alone (mean level of allogeneic chimerism 98%) were as susceptible as mixed chimeras to the tolerance-breaking effects of such inocula. The possible contribution of GVH reactivity to this resistance was investigated using an F1 into parent strain combination. In these animals, the use of non-TCD F1 BM inocula for reconstitution did not lead to resistance to the tolerance-breaking effects of recipient strain splenocytes.
- Research Organization:
- National Cancer Institute, Bethesda, MD (USA)
- OSTI ID:
- 6744843
- Journal Information:
- J. Exp. Med.; (United States), Vol. 168:2
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW
TRANSPLANTS
LYMPHOCYTES
BIOLOGICAL FUNCTIONS
CELL FLOW SYSTEMS
MICE
RADIATION CHIMERAS
SKIN
SPLEEN
SURVIVAL TIME
TOLERANCE
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
FUNCTIONS
HEMATOPOIETIC SYSTEM
LEUKOCYTES
MAMMALS
MATERIALS
MOSAICISM
ORGANS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals