Abstract
18 cloned T cell lines reactive with Borrelia burgdorferi proteins, all CD3+4+8-TCR-alpha/beta+ and restricted by HLA class II proteins, were isolated from four patients with chronic Lyme arthritis. Analysis of these T cell clones indicated that the T cell response to the Lyme disease spirochete is not oligoclonally restricted; yet all produced the same pattern of lymphokines, resembling that of murine type 1 T helper cells, after antigen-specific or nonspecific stimulation. Therefore, a subset of human CD4+ T cells, with a distinct profile of lymphokine secretion, is selectively activated by the pathogen inciting this chronic inflammatory disease.
Full Text
The Full Text of this article is available as a PDF (941.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
- Alvaro-Gracia J. M., Zvaifler N. J., Firestein G. S. Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. J Exp Med. 1989 Sep 1;170(3):865–875. doi: 10.1084/jem.170.3.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bacchetta R., de Waal Malefijt R., Yssel H., Abrams J., de Vries J. E., Spits H., Roncarolo M. G. Host-reactive CD4+ and CD8+ T cell clones isolated from a human chimera produce IL-5, IL-2, IFN-gamma and granulocyte/macrophage-colony-stimulating factor but not IL-4. J Immunol. 1990 Feb 1;144(3):902–908. [PubMed] [Google Scholar]
- Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
- Barthold S. W., Beck D. S., Hansen G. M., Terwilliger G. A., Moody K. D. Lyme borreliosis in selected strains and ages of laboratory mice. J Infect Dis. 1990 Jul;162(1):133–138. doi: 10.1093/infdis/162.1.133. [DOI] [PubMed] [Google Scholar]
- Bergström S., Bundoc V. G., Barbour A. G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol Microbiol. 1989 Apr;3(4):479–486. doi: 10.1111/j.1365-2958.1989.tb00194.x. [DOI] [PubMed] [Google Scholar]
- Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
- Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. doi: 10.1126/science.7043737. [DOI] [PubMed] [Google Scholar]
- Choi Y. W., Kotzin B., Herron L., Callahan J., Marrack P., Kappler J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8941–8945. doi: 10.1073/pnas.86.22.8941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins C., Peltz G. Immunoreactive epitopes on an expressed recombinant flagellar protein of Borrelia burgdorferi. Infect Immun. 1991 Feb;59(2):514–520. doi: 10.1128/iai.59.2.514-520.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Favre C., Wijdenes J., Cabrillat H., Djossou O., Banchereau J., de Vries J. E. Epitope mapping of recombinant human gamma interferon using monoclonal antibodies. Mol Immunol. 1989 Jan;26(1):17–25. doi: 10.1016/0161-5890(89)90015-1. [DOI] [PubMed] [Google Scholar]
- Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Heber-Katz E., Acha-Orbea H. The V-region disease hypothesis: evidence from autoimmune encephalomyelitis. Immunol Today. 1989 May;10(5):164–169. doi: 10.1016/0167-5699(89)90174-6. [DOI] [PubMed] [Google Scholar]
- Howe T. R., LaQuier F. W., Barbour A. G. Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit. Infect Immun. 1986 Oct;54(1):207–212. doi: 10.1128/iai.54.1.207-212.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappes D., Strominger J. L. Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem. 1988;57:991–1028. doi: 10.1146/annurev.bi.57.070188.005015. [DOI] [PubMed] [Google Scholar]
- Lewis D. B., Yu C. C., Meyer J., English B. K., Kahn S. J., Wilson C. B. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest. 1991 Jan;87(1):194–202. doi: 10.1172/JCI114970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maggi E., Del Prete G., Macchia D., Parronchi P., Tiri A., Chrétien I., Ricci M., Romagnani S. Profiles of lymphokine activities and helper function for IgE in human T cell clones. Eur J Immunol. 1988 Jul;18(7):1045–1050. doi: 10.1002/eji.1830180712. [DOI] [PubMed] [Google Scholar]
- Martin R., Howell M. D., Jaraquemada D., Flerlage M., Richert J., Brostoff S., Long E. O., McFarlin D. E., McFarland H. F. A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis. J Exp Med. 1991 Jan 1;173(1):19–24. doi: 10.1084/jem.173.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moller D. R., Konishi K., Kirby M., Balbi B., Crystal R. G. Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis. J Clin Invest. 1988 Oct;82(4):1183–1191. doi: 10.1172/JCI113715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
- Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
- Sakai K., Zamvil S. S., Mitchell D. J., Hodgkinson S., Rothbard J. B., Steinman L. Prevention of experimental encephalomyelitis with peptides that block interaction of T cells with major histocompatibility complex proteins. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9470–9474. doi: 10.1073/pnas.86.23.9470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaible U. E., Gay S., Museteanu C., Kramer M. D., Zimmer G., Eichmann K., Museteanu U., Simon M. M. Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. Am J Pathol. 1990 Oct;137(4):811–820. [PMC free article] [PubMed] [Google Scholar]
- Scott P., Pearce E., Cheever A. W., Coffman R. L., Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. doi: 10.1111/j.1600-065x.1989.tb00557.x. [DOI] [PubMed] [Google Scholar]
- Shanafelt M. C., Hindersson P., Soderberg C., Mensi N., Turck C. W., Webb D., Yssel H., Peltz G. T cell and antibody reactivity with the Borrelia burgdorferi 60-kDa heat shock protein in Lyme arthritis. J Immunol. 1991 Jun 1;146(11):3985–3992. [PubMed] [Google Scholar]
- Steere A. C., Dwyer E., Winchester R. Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles. N Engl J Med. 1990 Jul 26;323(4):219–223. doi: 10.1056/NEJM199007263230402. [DOI] [PubMed] [Google Scholar]
- Steere A. C., Schoen R. T., Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987 Nov;107(5):725–731. doi: 10.7326/0003-4819-107-5-725. [DOI] [PubMed] [Google Scholar]
- Street N. E., Mosmann T. R. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991 Feb;5(2):171–177. doi: 10.1096/fasebj.5.2.1825981. [DOI] [PubMed] [Google Scholar]
- Szczepanski A., Furie M. B., Benach J. L., Lane B. P., Fleit H. B. Interaction between Borrelia burgdorferi and endothelium in vitro. J Clin Invest. 1990 May;85(5):1637–1647. doi: 10.1172/JCI114615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urban J. L., Horvath S. J., Hood L. Autoimmune T cells: immune recognition of normal and variant peptide epitopes and peptide-based therapy. Cell. 1989 Oct 20;59(2):257–271. doi: 10.1016/0092-8674(89)90288-2. [DOI] [PubMed] [Google Scholar]
- Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
- Wierenga E. A., Snoek M., de Groot C., Chrétien I., Bos J. D., Jansen H. M., Kapsenberg M. L. Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients. J Immunol. 1990 Jun 15;144(12):4651–4656. [PubMed] [Google Scholar]
- Wraith D. C., McDevitt H. O., Steinman L., Acha-Orbea H. T cell recognition as the target for immune intervention in autoimmune disease. Cell. 1989 Jun 2;57(5):709–715. doi: 10.1016/0092-8674(89)90786-1. [DOI] [PubMed] [Google Scholar]
- Wucherpfennig K. W., Ota K., Endo N., Seidman J. G., Rosenzweig A., Weiner H. L., Hafler D. A. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25;248(4958):1016–1019. doi: 10.1126/science.1693015. [DOI] [PubMed] [Google Scholar]
- Yssel H., Nakamoto T., Schneider P., Freitas V., Collins C., Webb D., Mensi N., Soderberg C., Peltz G. Analysis of T lymphocytes cloned from the synovial fluid and blood of a patient with Lyme arthritis. Int Immunol. 1990;2(11):1081–1089. doi: 10.1093/intimm/2.11.1081. [DOI] [PubMed] [Google Scholar]
- Zhang Y., Schluep M., Frutiger S., Hughes G. J., Jeannet M., Steck A., Barkas T. Immunological heterogeneity of autoreactive T lymphocytes against the nicotinic acetylcholine receptor in myasthenic patients. Eur J Immunol. 1990 Dec;20(12):2577–2583. doi: 10.1002/eji.1830201208. [DOI] [PubMed] [Google Scholar]
