Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1988 Apr;56(4):744–750. doi: 10.1128/iai.56.4.744-750.1988

Characterization of efferent T suppressor cells induced by Paracoccidioides brasiliensis-specific afferent T suppressor cells.

B E Jimenez-Finkel 1, J W Murphy 1
PMCID: PMC259364  PMID: 2964412

Abstract

Previously, we reported that Paracoccidioides brasiliensis culture filtrate antigen (Pb.Ag) when injected i.v. into mice induces antigen-specific suppressor cells which down-regulate the anti-P. brasiliensis delayed-type hypersensitivity (DTH) response. The suppressor cells are present in both spleens and lymph nodes of Pb.Ag-treated animals and suppress the afferent limb but not the efferent limb of the DTH response to P. brasiliensis. The suppressor cells induced by Pb.Ag are L3T4+ Lyt-1+2- I-J+ T cells and are considered to be equivalent to the Ts1 cells described for other antigen-specific suppressor cell pathways. This report provides data which show that Ts1 cells induced by Pb.Ag or a soluble factor derived from Ts1 cells (TsF1) stimulates the production of second-order or efferent suppressor cells. The second-order suppressor cells are detectable in spleens and lymph nodes of mice 7 days after injection of Ts1 cells or TsF1 and are specific in suppressing the paracoccidioidal DTH response. In addition, the second-order suppressor cells are T cells with an L3T4- Lyt-2+ I-J+ phenotype and are effective in suppressing only the efferent limb of the P. brasiliensis DTH response. On the basis of the characteristics defined in this study, the paracoccidioidal second-order suppressor cells are equivalent to the Ts2 cells described for other antigen-specific suppressor-cell pathways. Thus, the suppressive circuit induced by Pb.Ag is similar to the suppressor-cell pathways that regulate the DTH responses to azobenzenearsonate, 4-hydroxy-3-nitrophenyl acetyl, lysozyme, and Cryptococcus neoformans antigen. We propose that such a suppressor-cell circuit as defined here with the murine model could be responsible for the depressed cell-mediated immune responses observed in paracoccidioidomycosis patients who have antigen circulating in their sera.

Full text

PDF
744

Selected References

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

  1. Adorini L., Colizzi V., Doria G., Ricciardi-Castagnoli P. Immunoregulation of lysozyme-specific suppression. II. Hen egg-white lysozyme-specific monoclonal suppressor T cell factor suppresses the afferent phase of delayed-type hypersensitivity and induces second-order suppressor T cells. Eur J Immunol. 1984 Sep;14(9):826–830. doi: 10.1002/eji.1830140911. [DOI] [PubMed] [Google Scholar]
  2. Asherson G. L., Colizzi V., Zembala M. An overview of T-suppressor cell circuits. Annu Rev Immunol. 1986;4:37–68. doi: 10.1146/annurev.iy.04.040186.000345. [DOI] [PubMed] [Google Scholar]
  3. Benacerraf B., Germain R. N. A single major pathway of T-lymphocyte interactions in antigen-specific immune suppression. Scand J Immunol. 1981;13(1):1–10. doi: 10.1111/j.1365-3083.1981.tb00104.x. [DOI] [PubMed] [Google Scholar]
  4. Brummer E., Restrepo A., Stevens D. A., Azzi R., Gomez A. M., Hoyos G. L., McEwen J. G., Cano L. E., de Bedout C. Murine model of paracoccidioidomycosis. Production of fatal acute pulmonary or chronic pulmonary and disseminated disease: immunological and pathological observations. J Exp Pathol. 1984 Summer;1(3):241–255. [PubMed] [Google Scholar]
  5. Cauley L. K., Murphy J. W. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect Immun. 1979 Mar;23(3):644–651. doi: 10.1128/iai.23.3.644-651.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crosson F. J., Jr, Winkelstein J. A., Moxon E. R. Enzyme-linked immunosorbent assay for detection and quantitation of capsular antigen of Haemophilus influenzae type b. Infect Immun. 1978 Nov;22(2):617–619. doi: 10.1128/iai.22.2.617-619.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Defaveri J., Rezkallah-Iwasso M. T., de Franco M. F. Experimental pulmonary paracoccidioidomycosis in mice: morphology and correlation of lesions with humoral and cellular immune response. Mycopathologia. 1982 Jan 15;77(1):3–11. doi: 10.1007/BF00588649. [DOI] [PubMed] [Google Scholar]
  8. Dietz M. H., Sy M. S., Greene M. I., Nisonoff A., Benacerraf B., Germain R. N. Antigen and receptor-driven regulatory mechanisms. VI. Demonstration of cross-reactive idiotypic determinants on azobenzenearsonate-specific antigen-binding suppressor T cells producing soluble suppressor factor(s). J Immunol. 1980 Dec;125(6):2374–2379. [PubMed] [Google Scholar]
  9. Dorf M. E., Benacerraf B. Suppressor cells and immunoregulation. Annu Rev Immunol. 1984;2:127–157. doi: 10.1146/annurev.iy.02.040184.001015. [DOI] [PubMed] [Google Scholar]
  10. Germain R. N., Theze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Antigen-specific T cell-mediated suppression. II. In vitro induction by I-J-coded L-glutamic acid50-L-tyrosine50 (GT)-specific T cell suppressor factor (GT-T8F) of suppressor T cells (T82) bearing distinct I-J determinants. J Immunol. 1978 Aug;121(2):602–607. [PubMed] [Google Scholar]
  11. Germain R. N., Thèze J., Kapp J. A., Benacerraf B. Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid60-L-alanine30-L-tyrosine10 specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen. J Exp Med. 1978 Jan 1;147(1):123–136. doi: 10.1084/jem.147.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoyos G. L., McEwen J. G., Brummer E., Castañeda E., Restrepo A., Stevens D. A. Chronic murine paracoccidioidomycosis: effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response. Sabouraudia. 1984;22(5):419–426. [PubMed] [Google Scholar]
  13. Jimenez-Finkel B. E., Murphy J. W. Induction of antigen-specific T suppressor cells by soluble Paracoccidioides brasiliensis antigen. Infect Immun. 1988 Apr;56(4):734–743. doi: 10.1128/iai.56.4.734-743.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  15. Khakpour F. R., Murphy J. W. Characterization of a third-order suppressor T cell (Ts3) induced by cryptococcal antigen(s). Infect Immun. 1987 Jul;55(7):1657–1662. doi: 10.1128/iai.55.7.1657-1662.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Mota N. G., Rezkallah-Iwasso M. T., Peraçoli M. T., Audi R. C., Mendes R. P., Marcondes J., Marques S. A., Dillon N. L., Franco M. F. Correlation between cell-mediated immunity and clinical forms of paracoccidioidomycosis. Trans R Soc Trop Med Hyg. 1985;79(6):765–772. doi: 10.1016/0035-9203(85)90112-9. [DOI] [PubMed] [Google Scholar]
  18. Murphy J. W., Moorhead J. W. Regulation of cell-mediated immunity in cryptococcosis. I. Induction of specific afferent T suppressor cells by cryptococcal antigen. J Immunol. 1982 Jan;128(1):276–283. [PubMed] [Google Scholar]
  19. Murphy J. W., Mosley R. L., Moorhead J. W. Regulation of cell-mediated immunity in cryptococcosis. II. Characterization of first-order T suppressor cells (Ts1) and induction of second-order suppressor cells. J Immunol. 1983 Jun;130(6):2876–2881. [PubMed] [Google Scholar]
  20. Murphy J. W., Mosley R. L. Regulation of cell-mediated immunity in cryptococcosis. III. Characterization of second-order T suppressor cells (Ts2). J Immunol. 1985 Jan;134(1):577–584. [PubMed] [Google Scholar]
  21. Musatti C. C., Rezkallah M. T., Mendes E., Mendes N. F. In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidiodomycosis. Cell Immunol. 1976 Jun 15;24(2):365–378. doi: 10.1016/0008-8749(76)90220-3. [DOI] [PubMed] [Google Scholar]
  22. Peraçoli M. T., Mota N. G., Montenegro M. R. Experimental paracoccidioidomycosis in the Syrian hamster. Morphology and correlation of lesions with humoral and cell-mediated immunity. Mycopathologia. 1982 Jul 23;79(1):7–17. doi: 10.1007/BF00636175. [DOI] [PubMed] [Google Scholar]
  23. Phanuphak P., Moorhead J. W., Claman H. N. Tolerance and contact sensitivity to DNFB in mice. II. Specific in vitro stimulation with a hapten, 2,4-dinitrobenzene sulfonic acid (DNB-SO3Na). J Immunol. 1974 Feb;112(2):849–851. [PubMed] [Google Scholar]
  24. Restrepo-Moreno A., Schneidau J. D., Jr Nature of the skin-reactive principle in culture filtrates prepared from Paracoccidioides brasiliensis. J Bacteriol. 1967 Jun;93(6):1741–1748. doi: 10.1128/jb.93.6.1741-1748.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Restrepo A., Restrepo M., de Restrepo F., Aristizábal L. H., Moncada L. H., Vélez H. Immune responses in paracoccidioidomycosis. A controlled study of 16 patients before and after treatment. Sabouraudia. 1978 Jun;16(2):151–163. [PubMed] [Google Scholar]
  26. Rodrigues M. C., Cassaguerra C. M., Lacaz C. da S. Antigenemia in paracoccidioidomycosis. Probable demonstration of circulating antigen by counterimmunoelectrophoresis test. Preliminary report. Rev Inst Med Trop Sao Paulo. 1984 Sep-Oct;26(5):285–287. doi: 10.1590/s0036-46651984000500011. [DOI] [PubMed] [Google Scholar]
  27. Sunday M. E., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VIII. Suppressor cell pathways in cutaneous sensitivity responses. J Exp Med. 1981 Apr 1;153(4):811–822. doi: 10.1084/jem.153.4.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weinberger J. Z., Germain R. N., Ju S. T., Greene M. I., Benacerraf B., Dorf M. E. Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. II. Demonstration of idiotypic determinants on suppressor T cells. J Exp Med. 1979 Oct 1;150(4):761–776. doi: 10.1084/jem.150.4.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. van Knapen F., Panggabean S. O. Detection of circulating antigen during acute infections with Toxoplasma gondii by enzyme-linked immunosorbent assay. J Clin Microbiol. 1977 Dec;6(6):545–547. doi: 10.1128/jcm.6.6.545-547.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES