Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus
- Kyushu Univ., Fukuoka (Japan)
Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr----AKR and C3H/lpr----AKR chimeras, CD4 single-positive thymocytes contained an increased number of V beta 6+ cells in spite of potentially deleting alleles of Mlsa, whereas V beta 6+ mature T cells were deleted in the MRL/+ ----AKR and C3H/+ ----AKR chimeras. There was no difference between MRL/+ ----AKR and MRL/lpr----AKR chimeras in their proportion of V beta 3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr----AKR chimeras, in particular in the forbidden V beta 6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.
- OSTI ID:
- 6144098
- Journal Information:
- Journal of Experimental Medicine; (USA), Vol. 173:1; ISSN 0022-1007
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW CELLS
TRANSPLANTS
IMMUNITY
RADIOINDUCTION
LYMPHOCYTES
CELL DIFFERENTIATION
GRAFT-HOST REACTION
LYMPHOKINES
MICE
RADIATION CHIMERAS
RECEPTORS
THYMUS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
GROWTH FACTORS
LEUKOCYTES
LYMPHATIC SYSTEM
MAMMALS
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MEMBRANE PROTEINS
MITOGENS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
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560152* - Radiation Effects on Animals- Animals