EVIDENCE THAT AN ANTHRACYCLINE-ANTI-CD8 IMMUNOCONJUGATE, IDARUBICIN-ANTI-LY-2.1, PROLONGS HEART ALLOGRAFT SURVIVAL IN MICE
| Autor: | G. J. A. Clunie, Geoffrey A. Pietersz, L. J. Purcell, Mark J. Smyth, Ian F. C. McKenzie, Patricia L Mottram |
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| Rok vydání: | 1993 |
| Předmět: |
Graft Rejection
Time Factors Transplantation Heterotopic Vena Cava Superior CD8 Antigens medicine.medical_treatment T cell Spleen Pharmacology Mice hemic and lymphatic diseases medicine Animals Antigens Ly Idarubicin Aorta Abdominal Mice Inbred BALB C Transplantation Chemotherapy business.industry Immunotoxins Graft Survival Antibodies Monoclonal Immunosuppression Skin Transplantation Immunoconjugate Mice Inbred C57BL medicine.anatomical_structure Immunology Mice Inbred CBA Heart Transplantation business CD8 medicine.drug |
| Zdroj: | Transplantation. 55:484-489 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-199303000-00006 |
| Popis: | To examine the potential use of immunoconjugates of drugs and antibodies as immunosuppressive agents, mice were treated with a short course (4 days) of T-cell-specific anti-Ly-2.1 monoclonal antibody, or MAB conjugated to an anthracycline, idarubicin (IDA). The anti-Ly-2.1 MAB had no significant effect on the survival of BALB/c (Ly-2.2) heart allografts in CBA (Ly-2.1) mice, but was a potent immunosuppressive agent when coupled to IDA, with most grafts surviving for > 100 days following treatment with doses ranging from 10 to 120 micrograms IDA, covalently coupled to 1-8 mg MAB. IDA-MAB treated mice with long-surviving heart grafts showed donor-specific tolerance. They did not reject donor-type skin grafts (these survived for > 50 days), but rejected third-party skin in 10-14 days. Heart allografts in these mice survived for > 100 days. Allografts placed 30 days after treatment were rejected, showing a recovery of peripheral T cell function at this time. Newly derived thymic T cells were, however, not required for this recovery since adult thymectomized, IDA-MAB treated animals also recovered T cell function and rejected heart allografts. FACScan analysis of T cells from mice treated with 80 micrograms IDA-4 mg MAB, which had received a heart allograft, showed 95% T cell depletion in the spleen compared with ungrafted, IDA-MAB treated animals, and untreated controls with or without allografts. Splenic T cell depletion was however not significant in CBA mice immunosuppressed with the lower dose of 10 micrograms IDA-MAB. Thus rapid depletion of splenic T cells was not required for immunosuppression induced by IDA-MAB conjugates. However, the minor subpopulation of Ly-2+, which was activated by alloantigen while carrying IDA-MAB, may be depleted during the T cell response to the allograft, resulting in a state of alloantigen-specific tolerance in mice with long-surviving heart allografts. |
| Databáze: | OpenAIRE |
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