Abstract
IVIg are increasingly used for the treatment of autoimmune diseases. In the present study, we show that IVIg contain antibodies directed against CD5, a cell surface molecule of T cells which is also a marker of the autoantibody-producing CD20+ ('B-1') subset of B lymphocytes. Antibodies to the CD5 molecule were demonstrated in IVIg by the ability of therapeutic preparations of IVIg to inhibit the binding of labelled CD5 MoAb to the CD5-expressing human T cell line H9. Preincubation of H9 cells with IVIg or with F(ab')2 fragments prepared from IVIg resulted in dose-dependent inhibition of the binding of CD5 antibody. The presence in IVIg of antibodies to the CD5 molecule was further confirmed by the binding of IVIg to mouse L cells that expressed human CD5 molecules following a stable transfection with CD5 cDNA. Human CD5 antibodies in IVIg provide therapeutic immunoglobulin preparations with the potential of modulating T cell functions through CD5, and of regulating the expression of B cell subsets expressing CD5. This may have implications for the treatment of autoimmune diseases.
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- Atlas E., Freedman J., Blanchette V., Kazatchkine M. D., Semple J. W. Downregulation of the anti-HLA alloimmune response by variable region-reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates. Blood. 1993 Jan 15;81(2):538–542. [PubMed] [Google Scholar]
- Avrameas S., Guilbert B., Dighiero G. Natural antibodies against tubulin, actin myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenström's macroglobulinemia may express similar antibody specificities. Ann Immunol (Paris) 1981 Mar-Apr;132C(2):231–236. doi: 10.1016/0769-2625(81)90031-3. [DOI] [PubMed] [Google Scholar]
- Avrameas S. Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton'. Immunol Today. 1991 May;12(5):154–159. doi: 10.1016/S0167-5699(05)80045-3. [DOI] [PubMed] [Google Scholar]
- Berneman A., Ternynck T., Avrameas S. Natural mouse IgG reacts with self antigens including molecules involved in the immune response. Eur J Immunol. 1992 Mar;22(3):625–633. doi: 10.1002/eji.1830220303. [DOI] [PubMed] [Google Scholar]
- Besa E. C. Use of intravenous immunoglobulin in chronic lymphocytic leukemia. Am J Med. 1984 Mar 30;76(3A):209–218. doi: 10.1016/0002-9343(84)90344-9. [DOI] [PubMed] [Google Scholar]
- Boumsell L., Coppin H., Pham D., Raynal B., Lemerle J., Dausset J., Bernard A. An antigen shared by a human T cell subset and B cell chronic lymphocytic leukemic cells. Distribution on normal and malignant lymphoid cells. J Exp Med. 1980 Jul 1;152(1):229–234. doi: 10.1084/jem.152.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bröker B. M., Klajman A., Youinou P., Jouquan J., Worman C. P., Murphy J., Mackenzie L., Quartey-Papafio R., Blaschek M., Collins P. Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies. J Autoimmun. 1988 Oct;1(5):469–481. doi: 10.1016/0896-8411(88)90068-6. [DOI] [PubMed] [Google Scholar]
- Burastero S. E., Casali P., Wilder R. L., Notkins A. L. Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med. 1988 Dec 1;168(6):1979–1992. doi: 10.1084/jem.168.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casali P., Burastero S. E., Nakamura M., Inghirami G., Notkins A. L. Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science. 1987 Apr 3;236(4797):77–81. doi: 10.1126/science.3105056. [DOI] [PubMed] [Google Scholar]
- Dauphinée M., Tovar Z., Talal N. B cells expressing CD5 are increased in Sjögren's syndrome. Arthritis Rheum. 1988 May;31(5):642–647. doi: 10.1002/art.1780310509. [DOI] [PubMed] [Google Scholar]
- Dietrich G., Algiman M., Sultan Y., Nydegger U. E., Kazatchkine M. D. Origin of anti-idiotypic activity against anti-factor VIII autoantibodies in pools of normal human immunoglobulin G (IVIg). Blood. 1992 Jun 1;79(11):2946–2951. [PubMed] [Google Scholar]
- Dietrich G., Kaveri S. V., Kazatchkine M. D. A V region-connected autoreactive subfraction of normal human serum immunoglobulin G. Eur J Immunol. 1992 Jul;22(7):1701–1706. doi: 10.1002/eji.1830220706. [DOI] [PubMed] [Google Scholar]
- Dietrich G., Kaveri S. V., Kazatchkine M. D. Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network. Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S73–S81. doi: 10.1016/0090-1229(92)90044-o. [DOI] [PubMed] [Google Scholar]
- Dwyer J. M. Manipulating the immune system with immune globulin. N Engl J Med. 1992 Jan 9;326(2):107–116. doi: 10.1056/NEJM199201093260206. [DOI] [PubMed] [Google Scholar]
- Fehr J., Hofmann V., Kappeler U. Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. N Engl J Med. 1982 May 27;306(21):1254–1258. doi: 10.1056/NEJM198205273062102. [DOI] [PubMed] [Google Scholar]
- Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
- Hurez V., Kaveri S. V., Kazatchkine M. D. Expression and control of the natural autoreactive IgG repertoire in normal human serum. Eur J Immunol. 1993 Apr;23(4):783–789. doi: 10.1002/eji.1830230402. [DOI] [PubMed] [Google Scholar]
- Iwata M., Shimozato T., Tokiwa H., Tsubura E. Antipyretic activity of a human immunoglobulin preparation for intravenous use in an experimental model of fever in rabbits. Infect Immun. 1987 Mar;55(3):547–554. doi: 10.1128/iai.55.3.547-554.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaveri S. V., Dietrich G., Hurez V., Kazatchkine M. D. Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases. Clin Exp Immunol. 1991 Nov;86(2):192–198. doi: 10.1111/j.1365-2249.1991.tb05794.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kipps T. J. The CD5 B cell. Adv Immunol. 1989;47:117–185. doi: 10.1016/s0065-2776(08)60663-x. [DOI] [PubMed] [Google Scholar]
- Kipps T. J., Vaughan J. H. Genetic influence on the levels of circulating CD5 B lymphocytes. J Immunol. 1987 Aug 15;139(4):1060–1064. [PubMed] [Google Scholar]
- Mackenzie L. E., Youinou P. Y., Hicks R., Yuksel B., Mageed R. A., Lydyard P. M. Auto- and polyreactivity of IgM from CD5+ and CD5- cord blood B cells. Scand J Immunol. 1991 Mar;33(3):329–335. doi: 10.1111/j.1365-3083.1991.tb01778.x. [DOI] [PubMed] [Google Scholar]
- Marchalonis J. J., Kaymaz H., Dedeoglu F., Schluter S. F., Yocum D. E., Edmundson A. B. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3325–3329. doi: 10.1073/pnas.89.8.3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murakami M., Tsubata T., Okamoto M., Shimizu A., Kumagai S., Imura H., Honjo T. Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice. Nature. 1992 May 7;357(6373):77–80. doi: 10.1038/357077a0. [DOI] [PubMed] [Google Scholar]
- Okamoto M., Murakami M., Shimizu A., Ozaki S., Tsubata T., Kumagai S., Honjo T. A transgenic model of autoimmune hemolytic anemia. J Exp Med. 1992 Jan 1;175(1):71–79. doi: 10.1084/jem.175.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rossi F., Guilbert B., Tonnelle C., Ternynck T., Fumoux F., Avrameas S., Kazatchkine M. D. Idiotypic interactions between normal human polyspecific IgG and natural IgM antibodies. Eur J Immunol. 1990 Sep;20(9):2089–2094. doi: 10.1002/eji.1830200930. [DOI] [PubMed] [Google Scholar]
- Shimozato T., Iwata M., Kawada H., Tamura N. Human immunoglobulin preparation for intravenous use induces elevation of cellular cyclic adenosine 3':5'-monophosphate levels, resulting in suppression of tumour necrosis factor alpha and interleukin-1 production. Immunology. 1991 Apr;72(4):497–501. [PMC free article] [PubMed] [Google Scholar]
- Suzuki N., Sakane T., Engleman E. G. Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus. J Clin Invest. 1990 Jan;85(1):238–247. doi: 10.1172/JCI114418. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsubakio T., Kurata Y., Katagiri S., Kanakura Y., Tamaki T., Kuyama J., Kanayama Y., Yonezawa T., Tarui S. Alteration of T cell subsets and immunoglobulin synthesis in vitro during high dose gamma-globulin therapy in patients with idiopathic thrombocytopenic purpura. Clin Exp Immunol. 1983 Sep;53(3):697–702. [PMC free article] [PubMed] [Google Scholar]
- Wacholtz M. C., Lipsky P. E. Treatment of lupus nephritis with CD5 PLUS, an immunoconjugate of an anti-CD5 monoclonal antibody and ricin A chain. Arthritis Rheum. 1992 Jul;35(7):837–839. doi: 10.1002/art.1780350721. [DOI] [PubMed] [Google Scholar]