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. 1989 Nov-Dec;62(6):565–577.

Photopheresis: a new therapeutic concept.

R L Edelson 1
PMCID: PMC2589156  PMID: 2700056

Abstract

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is a new treatment for disorders caused by aberrant T lymphocytes. It is now a standard therapy for advanced cutaneous T-cell lymphoma and shows promise in the treatment of two autoimmune disorders, pemphigus vulgaris and progressive systemic sclerosis (scleroderma). Additional diseases for which clinical trials are in progress include multiple sclerosis, organ transplant rejection, rheumatoid arthritis, and AIDS. The mechanism of action appears to involve a "vaccination" against the pathogenic T cells, in a clone-specific manner. Photoactivated 8-MOP initiates a cascade of immunologic events by forming covalent photoadducts with nuclear and cell surface-adherent DNA and possibly with other cellular molecules. For reasons not yet fully clarified, but probably related to enhanced cycling of the T-cell receptor for antigen, photopheresis increases the immunogenicity of the irradiated T cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the pathogenic clone(s). The specificity of the induced immunologic reaction probably results from the extremely disproportionate expansion of the pathogenic clone(s), relative to the several million other clones of normal T cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben-Nun A., Wekerle H., Cohen I. R. Vaccination against autoimmune encephalomyelitis with T-lymphocyte line cells reactive against myelin basic protein. Nature. 1981 Jul 2;292(5818):60–61. doi: 10.1038/292060a0. [DOI] [PubMed] [Google Scholar]
  2. Berger C. L., Cantor C., Welsh J., Dervan P., Begley T., Grant S., Gasparro F. P., Edelson R. L. Comparison of synthetic psoralen derivatives and 8-MOP in the inhibition of lymphocyte proliferation. Ann N Y Acad Sci. 1985;453:80–90. doi: 10.1111/j.1749-6632.1985.tb11800.x. [DOI] [PubMed] [Google Scholar]
  3. Berger C. L., Eisenberg A., Soper L., Chow J., Simone J., Gapas Y., Cacciapaglia B., Bennett L., Edelson R. L., Warburton D. Dual genotype in cutaneous T cell lymphoma: immunoglobulin gene rearrangement in clonal T cell malignancy. J Invest Dermatol. 1988 Jan;90(1):73–77. doi: 10.1111/1523-1747.ep12462574. [DOI] [PubMed] [Google Scholar]
  4. Berger C. L., Perez M., Laroche L., Edelson R. Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes. J Invest Dermatol. 1990 Jan;94(1):52–57. doi: 10.1111/1523-1747.ep12873349. [DOI] [PubMed] [Google Scholar]
  5. Edelson R. L. Cutaneous T cell lymphoma: mycosis fungoides, Sézary syndrome, and other variants. J Am Acad Dermatol. 1980 Feb;2(2):89–106. doi: 10.1016/s0190-9622(80)80385-9. [DOI] [PubMed] [Google Scholar]
  6. Edelson R., Berger C., Gasparro F., Jegasothy B., Heald P., Wintroub B., Vonderheid E., Knobler R., Wolff K., Plewig G. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987 Feb 5;316(6):297–303. doi: 10.1056/NEJM198702053160603. [DOI] [PubMed] [Google Scholar]
  7. Gasparro F. P., Saffran W. A., Cantor C. R., Edelson R. L. Wavelength dependence for AMT crosslinking of pBR322 DNA. Photochem Photobiol. 1984 Aug;40(2):215–219. doi: 10.1111/j.1751-1097.1984.tb04578.x. [DOI] [PubMed] [Google Scholar]
  8. Gilchrest B. A., Parrish J. A., Tanenbaum L., Haynes H. A., Fitzpatrick T. B. Oral methoxsalen photochemotherapy of mycosis fungoides. Cancer. 1976 Aug;38(2):683–689. doi: 10.1002/1097-0142(197608)38:2<683::aid-cncr2820380210>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  9. Holoshitz J., Naparstek Y., Ben-Nun A., Cohen I. R. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science. 1983 Jan 7;219(4580):56–58. doi: 10.1126/science.6336851. [DOI] [PubMed] [Google Scholar]
  10. Kraemer K. H. In vitro assay of the effects of psoralens plus ultraviolet radiation on human lymphoid cells. J Natl Cancer Inst. 1982 Jul;69(1):219–227. [PubMed] [Google Scholar]
  11. LERNER A. B., DENTON C. R., FITZPATRICK T. B. Clinical and experimental studies with 8-methoxypsoralen in vitiligo. J Invest Dermatol. 1953 Apr;20(4):299–314. doi: 10.1038/jid.1953.36. [DOI] [PubMed] [Google Scholar]
  12. Lamberg S. I., Green S. B., Byar D. P., Block J. B., Clendenning W. E., Douglas M. C., Epstein E. H., Jr, Fuks Z. Y., Golitz L. E., Lorincz A. L. Clinical staging for cutaneous T-cell lymphoma. Ann Intern Med. 1984 Feb;100(2):187–192. doi: 10.7326/0003-4819-100-2-187. [DOI] [PubMed] [Google Scholar]
  13. Lider O., Reshef T., Beraud E., Ben-Nun A., Cohen I. R. Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science. 1988 Jan 8;239(4836):181–183. doi: 10.1126/science.2447648. [DOI] [PubMed] [Google Scholar]
  14. Morison W. L., Parrish J. A., McAuliffe D. J., Bloch K. J. Sensitivity of mononuclear cells to PUVA: effect on subsequent stimulation with mitogens and on exclusion of trypan blue dye. Clin Exp Dermatol. 1981 May;6(3):273–277. doi: 10.1111/j.1365-2230.1981.tb02303.x. [DOI] [PubMed] [Google Scholar]
  15. Parrish J. A., Fitzpatrick T. B., Tanenbaum L., Pathak M. A. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med. 1974 Dec 5;291(23):1207–1211. doi: 10.1056/NEJM197412052912301. [DOI] [PubMed] [Google Scholar]
  16. Perez M., Edelson R., Laroche L., Berger C. Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes. J Invest Dermatol. 1989 May;92(5):669–676. doi: 10.1111/1523-1747.ep12696853. [DOI] [PubMed] [Google Scholar]
  17. Santella R. M., Dharmaraja N., Gasparro F. P., Edelson R. L. Monoclonal antibodies to DNA modified by 8-methoxypsoralen and ultraviolet A light. Nucleic Acids Res. 1985 Apr 11;13(7):2533–2544. doi: 10.1093/nar/13.7.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Song P. S., Tapley K. J., Jr Photochemistry and photobiology of psoralens. Photochem Photobiol. 1979 Jun;29(6):1177–1197. doi: 10.1111/j.1751-1097.1979.tb07838.x. [DOI] [PubMed] [Google Scholar]
  19. Walter J. F., Kelsey W. H., Voorhees J. J., Duell E. A. Psoralen plus black light inhibits epidermal DNA synthesis. Arch Dermatol. 1973 Jun;107(6):861–865. [PubMed] [Google Scholar]
  20. Yemul S., Berger C., Estabrook A., Suarez S., Edelson R., Bayley H. Selective killing of T lymphocytes by phototoxic liposomes. Proc Natl Acad Sci U S A. 1987 Jan;84(1):246–250. doi: 10.1073/pnas.84.1.246. [DOI] [PMC free article] [PubMed] [Google Scholar]

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