Abstract
1. A local graft versus host reaction in rats permits the evaluation of drug action on (i) donor (parental) animals and (ii) recipient animals (F1 hybrid) prior to establishing a lymphoid cell graft to detect drugs which might attenuate immunocompetence over a prolonged period (e.g. steroids).
2. Treatment of the recipient animals after a lymphoid graft readily detects anti-proliferative agents and may disclose other agents which interfere with the recognition of non-self by viable graft cells.
3. Treatment of the cell graft in vitro before innoculation into the recipient animal permits the detection of alkylating agents, which effectively deactivate graft cells at non-toxic concentrations.
4. Examples are given of how this reaction may be used to evaluate functionally the effects of chemical modification of the cell surfaces of lymphocytes and to detect active metabolites generated from a precursor drug (e.g. cyclophosphamide).
5. Some novel immunosuppressant drugs are described.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Darzynkiewicz Z., Pieńkowski M. Effect of prednisolone on RNA synthesis in human lymphocytes stimulated by phytohaemagglutinin. Exp Cell Res. 1969 Feb;54(2):289–292. doi: 10.1016/0014-4827(69)90257-2. [DOI] [PubMed] [Google Scholar]
- Davies G. E. Immunosuppressive activity of 3-acetyl-5-(4-fluorobenzylidene)-4-hydroxy-2-oxo-2:5-dihydrothiophen (I.C.I. 47,776). Immunology. 1968 Mar;14(3):393–399. [PMC free article] [PubMed] [Google Scholar]
- FOX M., HOWARD J. G. An acquired type of refractoriness to graft-versus-host reaction in adult F1 hybrid mice. Transplantation. 1963 Jan;1:2–14. doi: 10.1097/00007890-196301010-00002. [DOI] [PubMed] [Google Scholar]
- Ford W. L., Burr W., Simonsen M. A lymph node weight assay for the graft-versus-host activity of rat lymphoid cells. Transplantation. 1970 Sep;10(3):258–266. doi: 10.1097/00007890-197009000-00007. [DOI] [PubMed] [Google Scholar]
- Levine S. Local and regional forms of graft-versus-host disease in lymph nodes. Transplantation. 1968 Sep;6(6):799–802. doi: 10.1097/00007890-196809000-00009. [DOI] [PubMed] [Google Scholar]
- Levy L. A contribution to the mechanism of drug inhibition of the graft vs host reaction. J Reticuloendothel Soc. 1973 Jan;13(1):1–6. [PubMed] [Google Scholar]
- O'Mant D. M. The preparation and chemical properties of 3-acyl-5-arylidene-4-hydroxy-2,5-dihydro-2-oxothiophens, a new class of immunosuppressive agent. J Chem Soc Perkin 1. 1968;12:1501–1505. doi: 10.1039/j39680001501. [DOI] [PubMed] [Google Scholar]
- UDENFRIEND S., CLARK C. T., AXELROD J., BRODIE B. B. Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation. J Biol Chem. 1954 Jun;208(2):731–739. [PubMed] [Google Scholar]
- Volkman A. The host cell response in the local graft-versus-host reaction induced in the kidneys of F 1 rats by parental thoracic duct lymphocytes. J Exp Med. 1972 Jul 1;136(1):21–38. doi: 10.1084/jem.136.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshida Y., Osmond D. G. Graft-versus-host activity of rat bone marrow, marrow fractions, and lymphoid tissues quantitated by a popliteal lymph node weight assay. Transplantation. 1971 Aug;12(2):121–129. doi: 10.1097/00007890-197108000-00004. [DOI] [PubMed] [Google Scholar]
- Zatz M. M., Goldstein A. L., Blumenfeld O. O., White A. Regulation of normal and leukaemic lymphocyte transformation and recirculation by sodium periodate oxidation and sodium borohydride reduction. Nat New Biol. 1972 Dec 20;240(103):252–255. doi: 10.1038/newbio240252a0. [DOI] [PubMed] [Google Scholar]