Abstract
The immunopathologic sequelae of chlamydial infection are correlated with immune responses to the Chlamydia trachomatis heat shock protein 60 (hsp60). One pathogenic mechanism that may explain this association is the induction of autoimmune responses to self hsp60, since these two proteins share a high degree of amino acid sequence identity. To investigate the conditions under which autoimmune responses can be generated against self hsp60, groups of CBA mice were immunized with recombinant mouse hsp60, recombinant chlamydial hsp60, or both proteins. The data show that autoimmune responses characterized by strong T-cell proliferation and high titers of antibody to self hsp60 are induced only by concurrent immunization with mouse and chlamydial hsp60. Immunization with mouse hsp60 alone induced lymphocytes that secreted high levels of interleukin-10 (IL-10) but did not proliferate in response to in vitro stimulation with mouse hsp60; coimmunization with mouse and chlamydial hsp60s induced lymphocytes that proliferated strongly in response to mouse hsp60, secreted 6-fold less IL-10, and exhibited a 12-fold increase in the ratio of gamma interferon/IL-10 production. Switches in cytokine production patterns may mediate the pathogenesis of hsp60-associated diseases such as C. trachomatis immunopathology.
Full Text
The Full Text of this article is available as a PDF (183.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boog C. J., de Graeff-Meeder E. R., Lucassen M. A., van der Zee R., Voorhorst-Ogink M. M., van Kooten P. J., Geuze H. J., van Eden W. Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J Exp Med. 1992 Jun 1;175(6):1805–1810. doi: 10.1084/jem.175.6.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunham R. C., Peeling R. W. Chlamydia trachomatis antigens: role in immunity and pathogenesis. Infect Agents Dis. 1994 Oct;3(5):218–233. [PubMed] [Google Scholar]
- Cerrone M. C., Ma J. J., Stephens R. S. Cloning and sequence of the gene for heat shock protein 60 from Chlamydia trachomatis and immunological reactivity of the protein. Infect Immun. 1991 Jan;59(1):79–90. doi: 10.1128/iai.59.1.79-90.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Y., Kuchroo V. K., Inobe J., Hafler D. A., Weiner H. L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994 Aug 26;265(5176):1237–1240. doi: 10.1126/science.7520605. [DOI] [PubMed] [Google Scholar]
- Ding L., Shevach E. M. IL-10 inhibits mitogen-induced T cell proliferation by selectively inhibiting macrophage costimulatory function. J Immunol. 1992 May 15;148(10):3133–3139. [PubMed] [Google Scholar]
- Elias D., Reshef T., Birk O. S., van der Zee R., Walker M. D., Cohen I. R. Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3088–3091. doi: 10.1073/pnas.88.8.3088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elsaghier A., Prantera C., Bothamley G., Wilkins E., Jindal S., Ivanyi J. Disease association of antibodies to human and mycobacterial hsp70 and hsp60 stress proteins. Clin Exp Immunol. 1992 Aug;89(2):305–309. doi: 10.1111/j.1365-2249.1992.tb06950.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enk A. H., Angeloni V. L., Udey M. C., Katz S. I. Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. J Immunol. 1993 Sep 1;151(5):2390–2398. [PubMed] [Google Scholar]
- Enk A. H., Saloga J., Becker D., Mohamadzadeh M., Knop J. Induction of hapten-specific tolerance by interleukin 10 in vivo. J Exp Med. 1994 Apr 1;179(4):1397–1402. doi: 10.1084/jem.179.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evavold B. D., Allen P. M. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science. 1991 May 31;252(5010):1308–1310. doi: 10.1126/science.1833816. [DOI] [PubMed] [Google Scholar]
- Fernandez-Botran R., Sanders V. M., Mosmann T. R., Vitetta E. S. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med. 1988 Aug 1;168(2):543–558. doi: 10.1084/jem.168.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freedman A. S., Freeman G. J., Rhynhart K., Nadler L. M. Selective induction of B7/BB-1 on interferon-gamma stimulated monocytes: a potential mechanism for amplification of T cell activation through the CD28 pathway. Cell Immunol. 1991 Oct 15;137(2):429–437. doi: 10.1016/0008-8749(91)90091-o. [DOI] [PubMed] [Google Scholar]
- Hendrick J. P., Hartl F. U. Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem. 1993;62:349–384. doi: 10.1146/annurev.bi.62.070193.002025. [DOI] [PubMed] [Google Scholar]
- Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
- Lin R. H., Mamula M. J., Hardin J. A., Janeway C. A., Jr Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991 Jun 1;173(6):1433–1439. doi: 10.1084/jem.173.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linsley P. S., Brady W., Grosmaire L., Aruffo A., Damle N. K., Ledbetter J. A. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med. 1991 Mar 1;173(3):721–730. doi: 10.1084/jem.173.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mabey D. C., Bailey R. L., Dunn D., Jones D., Williams J. H., Whittle H. C., Ward M. E. Expression of MHC class II antigens by conjunctival epithelial cells in trachoma: implications concerning the pathogenesis of blinding disease. J Clin Pathol. 1991 Apr;44(4):285–289. doi: 10.1136/jcp.44.4.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
- Morrison R. P., Belland R. J., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med. 1989 Oct 1;170(4):1271–1283. doi: 10.1084/jem.170.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Röcken M., Shevach E. M. Immune deviation--the third dimension of nondeletional T cell tolerance. Immunol Rev. 1996 Feb;149:175–194. doi: 10.1111/j.1600-065x.1996.tb00904.x. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. Acquisition of immunologic self-tolerance. Cell. 1989 Jun 30;57(7):1073–1081. doi: 10.1016/0092-8674(89)90044-5. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. Models of T cell anergy: is there a common molecular mechanism? J Exp Med. 1996 Jul 1;184(1):1–8. doi: 10.1084/jem.184.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Taga K., Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992 Feb 15;148(4):1143–1148. [PubMed] [Google Scholar]
- Venner T. J., Gupta R. S. Nucleotide sequence of mouse HSP60 (chaperonin, GroEL homolog) cDNA. Biochim Biophys Acta. 1990 Nov 30;1087(3):336–338. doi: 10.1016/0167-4781(90)90008-p. [DOI] [PubMed] [Google Scholar]
- Viale A. M., Arakaki A. K., Soncini F. C., Ferreyra R. G. Evolutionary relationships among eubacterial groups as inferred from GroEL (chaperonin) sequence comparisons. Int J Syst Bacteriol. 1994 Jul;44(3):527–533. doi: 10.1099/00207713-44-3-527. [DOI] [PubMed] [Google Scholar]
- Windhagen A., Scholz C., Höllsberg P., Fukaura H., Sette A., Hafler D. A. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity. 1995 Apr;2(4):373–380. doi: 10.1016/1074-7613(95)90145-0. [DOI] [PubMed] [Google Scholar]
- Yang X., HayGlass K. T., Brunham R. C. Genetically determined differences in IL-10 and IFN-gamma responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection. J Immunol. 1996 Jun 1;156(11):4338–4344. [PubMed] [Google Scholar]
- Yi Y., Zhong G., Brunham R. C. Continuous B-cell epitopes in Chlamydia trachomatis heat shock protein 60. Infect Immun. 1993 Mar;61(3):1117–1120. doi: 10.1128/iai.61.3.1117-1120.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Graeff-Meeder E. R., Rijkers G. T., Voorhorst-Ogink M. M., Kuis W., van der Zee R., van Eden W., Zegers B. J. Antibodies to human HSP60 in patients with juvenile chronic arthritis, diabetes mellitus, and cystic fibrosis. Pediatr Res. 1993 Oct;34(4):424–428. doi: 10.1203/00006450-199310000-00008. [DOI] [PubMed] [Google Scholar]
- de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- el-Asrar A. M., Van den Oord J. J., Geboes K., Missotten L., Emarah M. H., Desmet V. Immunopathology of trachomatous conjunctivitis. Br J Ophthalmol. 1989 Apr;73(4):276–282. doi: 10.1136/bjo.73.4.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Eden W., Thole J. E., van der Zee R., Noordzij A., van Embden J. D., Hensen E. J., Cohen I. R. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature. 1988 Jan 14;331(6152):171–173. doi: 10.1038/331171a0. [DOI] [PubMed] [Google Scholar]