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. 1993 Nov;61(11):4750–4759. doi: 10.1128/iai.61.11.4750-4759.1993

Cytokine profiles associated with induction of the anticryptococcal cell-mediated immune response.

J W Murphy 1
PMCID: PMC281230  PMID: 8406874

Abstract

Previous studies with a murine model have shown that immunization with cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund adjuvant (CFA) induces two populations of anticryptococcal reactive CD4+ T cells. One population (TDH cells) transfers anticryptococcal delayed-type hypersensitivity (DTH), and the other population (Tamp cells) amplifies the anticryptococcal DTH response of given to recipient mice at the time of immunization of the recipient. Treatment of mice with cyclosporin A (CsA) ablates the induction of Tamp cells but not TDH cells. The present study focused on assessing the cytokines produced by spleen cells taken from CsA-treated and control (solvent-treated) mice at days 1, 2, 4, and 6 after immunization. Supernatants from the spleen cells cultured in vitro for 24 or 48 h in medium alone or with CneF, concanavalin A, or phorbol 12-myristate 13-acetate plus calcium ionophore were assessed for the presence of interleukin-2 (IL-2), gamma interferon (IFN-gamma), IL-4, IL-5, and tumor necrosis factor. Spleen cells from CneF-CFA-treated mice produced IL-2 and IFN-gamma, but not IL-4 or IL-5, constitutively and in response to CneF, indicating that CneF-CFA induces a Th1 response. Tumor necrosis factor was not produced. Anticryptococcal TDH cells developed in spleens in which there were low levels of IFN-gamma and IL-2 (CsA-treated, immunized mice), whereas anticryptococcal Tamp cells along with TDH cells matured in spleens in which production of IFN-gamma and IL-2 was high (solvent-treated, immunized mice). The data also suggest that IL-2 and IFN-gamma produced by Tamp cells early after adoptive transfer are influential in the development of the amplified anticryptococcal DTH response that has been observed in Tamp cell-recipient mice.

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Selected References

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  1. 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]
  2. Bloom B. R., Modlin R. L., Salgame P. Stigma variations: observations on suppressor T cells and leprosy. Annu Rev Immunol. 1992;10:453–488. doi: 10.1146/annurev.iy.10.040192.002321. [DOI] [PubMed] [Google Scholar]
  3. Buchanan K. L., Fidel P. L., Jr, Murphy J. W. Effects of Cryptococcus neoformans-specific suppressor T cells on the amplified anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1991 Jan;59(1):29–35. doi: 10.1128/iai.59.1.29-35.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buchanan K. L., Murphy J. W. Characterization of cellular infiltrates and cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1993 Jul;61(7):2854–2865. doi: 10.1128/iai.61.7.2854-2865.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cher D. J., Mosmann T. R. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed] [Google Scholar]
  6. Chuck S. L., Sande M. A. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med. 1989 Sep 21;321(12):794–799. doi: 10.1056/NEJM198909213211205. [DOI] [PubMed] [Google Scholar]
  7. Fidel P. L., Jr, Murphy J. W. Characterization of a cell population which amplifies the anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1990 Feb;58(2):393–398. doi: 10.1128/iai.58.2.393-398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fidel P. L., Jr, Murphy J. W. Effects of cyclosporin A on the cells responsible for the anticryptococcal cell-mediated immune response and its regulation. Infect Immun. 1989 Apr;57(4):1158–1164. doi: 10.1128/iai.57.4.1158-1164.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fong T. A., Mosmann T. R. The role of IFN-gamma in delayed-type hypersensitivity mediated by Th1 clones. J Immunol. 1989 Nov 1;143(9):2887–2893. [PubMed] [Google Scholar]
  10. Gajewski T. F., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed] [Google Scholar]
  11. Gimmi C. D., Freeman G. J., Gribben J. G., Sugita K., Freedman A. S., Morimoto C., Nadler L. M. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6575–6579. doi: 10.1073/pnas.88.15.6575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grzych J. M., Pearce E., Cheever A., Caulada Z. A., Caspar P., Heiny S., Lewis F., Sher A. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol. 1991 Feb 15;146(4):1322–1327. [PubMed] [Google Scholar]
  13. Issekutz T. B., Stoltz J. M., van der Meide P. The recruitment of lymphocytes into the skin by T cell lymphokines: the role of gamma-interferon. Clin Exp Immunol. 1988 Jul;73(1):70–75. [PMC free article] [PubMed] [Google Scholar]
  14. Issekutz T. B., Stoltz J. M., vd Meide P. Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-gamma. J Immunol. 1988 May 1;140(9):2989–2993. [PubMed] [Google Scholar]
  15. June C. H., Ledbetter J. A., Gillespie M. M., Lindsten T., Thompson C. B. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 1987 Dec;7(12):4472–4481. doi: 10.1128/mcb.7.12.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Koulova L., Clark E. A., Shu G., Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med. 1991 Mar 1;173(3):759–762. doi: 10.1084/jem.173.3.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kovacs J. A., Kovacs A. A., Polis M., Wright W. C., Gill V. J., Tuazon C. U., Gelmann E. P., Lane H. C., Longfield R., Overturf G. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Oct;103(4):533–538. doi: 10.7326/0003-4819-103-4-533. [DOI] [PubMed] [Google Scholar]
  19. Krönke M., Leonard W. J., Depper J. M., Arya S. K., Wong-Staal F., Gallo R. C., Waldmann T. A., Greene W. C. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214–5218. doi: 10.1073/pnas.81.16.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Larrick J. W., Wright S. C. Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J. 1990 Nov;4(14):3215–3223. doi: 10.1096/fasebj.4.14.2172061. [DOI] [PubMed] [Google Scholar]
  21. Lim T. S., Murphy J. W., Cauley L. K. Host-etiological agent interactions in intranasally and intraperitoneally induced Cryptococcosis in mice. Infect Immun. 1980 Aug;29(2):633–641. doi: 10.1128/iai.29.2.633-641.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lim T. S., Murphy J. W. Transfer of immunity to cryptococcosis by T-enriched splenic lymphocytes from Cryptococcus neoformans-sensitized mice. Infect Immun. 1980 Oct;30(1):5–11. doi: 10.1128/iai.30.1.5-11.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  24. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  25. Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
  26. Murphy J. W., Cozad G. C. Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique. Infect Immun. 1972 Jun;5(6):896–901. doi: 10.1128/iai.5.6.896-901.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy J. W. Effects of first-order Cryptococcus-specific T-suppressor cells on induction of cells responsible for delayed-type hypersensitivity. Infect Immun. 1985 May;48(2):439–445. doi: 10.1128/iai.48.2.439-445.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murphy J. W. Immunoregulation in cryptococcosis. Immunol Ser. 1989;47:319–345. [PubMed] [Google Scholar]
  29. 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]
  30. Murphy J. W., Pahlavan N. Cryptococcal culture filtrate antigen for detection of delayed-type hypersensitivity in cryptococcosis. Infect Immun. 1979 Jul;25(1):284–292. doi: 10.1128/iai.25.1.284-292.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nowak T. P., Barondes S. H. Agglutinin from Limulus polyphemus. Purification with formalinized horse erythrocytes as the affinity adsorbent. Biochim Biophys Acta. 1975 May 30;393(1):115–123. [PubMed] [Google Scholar]
  32. Pearce E. J., Caspar P., Grzych J. M., Lewis F. A., Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991 Jan 1;173(1):159–166. doi: 10.1084/jem.173.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pennington J. E. Pseudomonas aeruginosa immunotherapy. Eur J Clin Microbiol Infect Dis. 1990 Jun;9(6):377–380. doi: 10.1007/BF01979465. [DOI] [PubMed] [Google Scholar]
  34. Sigal N. H., Dumont F. J. Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol. 1992;10:519–560. doi: 10.1146/annurev.iy.10.040192.002511. [DOI] [PubMed] [Google Scholar]

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