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), Journal Name: Journal of Experimental Medicine; (USA) Vol. 173:1; ISSN 0022-1007; ISSN JEMEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW CELLS
CELL DIFFERENTIATION
CHIMERAS
CONNECTIVE TISSUE CELLS
GRAFT-HOST REACTION
GROWTH FACTORS
IMMUNITY
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MICE
MITOGENS
MOSAICISM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIATION CHIMERAS
RADIOINDUCTION
RECEPTORS
RODENTS
SOMATIC CELLS
THYMUS
TRANSPLANTS
VERTEBRATES