Immunodeficiency in RFM/(T6xRFM)F1 mouse chimaeras with lethal host-versus-graft syndrome
| Autor: | J. L. Montour, R. C. Hard, B. A. Fuchs |
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| Rok vydání: | 1995 |
| Předmět: |
Time Factors
T-Lymphocytes Lymphocyte Immunology Mice Inbred Strains Spleen Biology Lymphocyte Activation Clonal deletion Mice Immune system medicine Animals Immunology and Allergy Lymphocytes Immunodeficiency B cell Chimera Immunologic Deficiency Syndromes Organ Size medicine.disease medicine.anatomical_structure Host vs Graft Reaction Bone marrow Lymphocyte Culture Test Mixed Central tolerance Research Article |
| Zdroj: | Clinical and Experimental Immunology. 100:352-358 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.1995.tb03676.x |
| Popis: | SUMMARY Rather than central tolerance, the perinatal inoculation of related F1 hybrid spleen cells into inbred mice may result in host-versus-graft (HVG) reactions manifested as transient autoimmunity, or as a lethal immunodeficiency syndrome. RFM/(T6xRFM)F1 chimaeras with lethal disease die in 30 days with lymphosplenomegaly, immune complexes and impaired immune responses. The present studies used in vitro proliferation assays to show that the HVG reaction caused hyperplasia sufficient to account for the lymphosplenomegaly, while also causing severe impairment of splenic and nodal cell responses to concanavalin A (Con A) and to bacterial lipopolysaccharide (LPS). By 25 days, HVG mice could not distinguish between self and non-self as judged by mixed lymphocyte reactions (MLR) to RFM, (T6xRFM)F1 and third party A/J cells. There were no indications that host cells reactive to F1 donor cells had undergone clonal deletion, anergy or expansion. Flow cytometry revealed that donor T lymphocytes achieved stable engraftment, mostly in the nodes, despite the HVG reaction. Taken together with previous observations, these studies showed that HVG reactions in young parent F1/chimaeras can result in an immunodeficiency state which is characterized by an early appearing, profound and persistent impairment of both host and donor T and B cell functions. The results suggest that HVG reactions can contribute directly to immune deficits seen after clinical allogeneic bone marrow transplantation. |
| Databáze: | OpenAIRE |
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