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. 1997 Feb;90(2):189–197. doi: 10.1046/j.1365-2567.1997.00144.x

Kinetics of cellular infiltration and cytokine production during the efferent phase of a delayed-type hypersensitivity reaction.

K L Buchanan 1, J W Murphy 1
PMCID: PMC1456754  PMID: 9135546

Abstract

Cell-mediated immunity is a primary host resistance mechanism against many infectious organisms and is responsible for leucocyte recruitment to the infection site. Delayed-type hypersensitivity (DTH) reactions are in vivo correlates of cell-mediated immunity and have long been used to assess the level of cell-mediated immune (CMI) responsiveness to specific antigens. It has been difficult to study the kinetics of cellular influx and cytokine composition at the site of an on-going CMI reaction. Consequently, knowledge of the sequential events occurring during the efferent phase of a CMI response is incomplete. Here we report on the use of a gelatin sponge model for evaluating the progression of events during the effector phase of a DTH reaction to antigens of the mycotic organism Cryptococcus neoformans. Previously, we have shown that 24 hr after antigen injection into sponges in infected or immune mice, the leucocyte types infiltrating the sponges are consistent with a classical murine DTH reaction. Through kinetic studies, we show here that neutrophils are the first leucocytes to appear in DTH-reactive sponges, followed by increases in lymphocyte and then monocyte numbers. Tumour necrosis factor (TNF), interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and IL-5 were elevated in DTH-reactive sponges compared with control sponges, and each cytokine had a relatively unique temporal profile. IL-4 was not detectable in the sponges. Together our data indicate that the expression of a CMI response comprises a well-regulated sequential influx of leucocytes that contribute to the lymphokine composition of the reaction.

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Selected References

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  1. Barnes P. F., Lu S., Abrams J. S., Wang E., Yamamura M., Modlin R. L. Cytokine production at the site of disease in human tuberculosis. Infect Immun. 1993 Aug;61(8):3482–3489. doi: 10.1128/iai.61.8.3482-3489.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bromberg J. S., Chavin K. D., Kunkel S. L. Anti-tumor necrosis factor antibodies suppress cell-mediated immunity in vivo. J Immunol. 1992 Jun 1;148(11):3412–3417. [PubMed] [Google Scholar]
  3. 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]
  4. Buchanan K. L., Murphy J. W. Regulation of cytokine production during the expression phase of the anticryptococcal delayed-type hypersensitivity response. Infect Immun. 1994 Jul;62(7):2930–2939. doi: 10.1128/iai.62.7.2930-2939.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherniak R. Soluble polysaccharides of Cryptococcus neoformans. Curr Top Med Mycol. 1988;2:40–54. doi: 10.1007/978-1-4612-3730-3_2. [DOI] [PubMed] [Google Scholar]
  6. Devi S., Laning J., Luo Y., Dorf M. E. Biologic activities of the beta-chemokine TCA3 on neutrophils and macrophages. J Immunol. 1995 May 15;154(10):5376–5383. [PubMed] [Google Scholar]
  7. Doherty M. L., Bassett H. F., Quinn P. J., Davis W. C., Kelly A. P., Monaghan M. L. A sequential study of the bovine tuberculin reaction. Immunology. 1996 Jan;87(1):9–14. [PMC free article] [PubMed] [Google Scholar]
  8. Faccioli L. H., Souza G. E., Cunha F. Q., Poole S., Ferreira S. H. Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms. Agents Actions. 1990 Jun;30(3-4):344–349. doi: 10.1007/BF01966298. [DOI] [PubMed] [Google Scholar]
  9. Flesch I. E., Schwamberger G., Kaufmann S. H. Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans. J Immunol. 1989 May 1;142(9):3219–3224. [PubMed] [Google Scholar]
  10. 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]
  11. Hidore M. R., Nabavi N., Sonleitner F., Murphy J. W. Murine natural killer cells are fungicidal to Cryptococcus neoformans. Infect Immun. 1991 May;59(5):1747–1754. doi: 10.1128/iai.59.5.1747-1754.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Higashi N., Yoshizuka N., Ohuchi A., Osawa T., Kobayashi Y. Involvement of inflammatory cytokines in a delayed-type hypersensitivity reaction. Cell Immunol. 1995 Apr 1;161(2):288–294. doi: 10.1006/cimm.1995.1038. [DOI] [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. Kasama T., Strieter R. M., Lukacs N. W., Lincoln P. M., Burdick M. D., Kunkel S. L. Interferon gamma modulates the expression of neutrophil-derived chemokines. J Investig Med. 1995 Feb;43(1):58–67. [PubMed] [Google Scholar]
  16. Levitz S. M., DiBenedetto D. J. Differential stimulation of murine resident peritoneal cells by selectively opsonized encapsulated and acapsular Cryptococcus neoformans. Infect Immun. 1988 Oct;56(10):2544–2551. doi: 10.1128/iai.56.10.2544-2551.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Levitz S. M., Dupont M. P. Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro. J Clin Invest. 1993 Apr;91(4):1490–1498. doi: 10.1172/JCI116354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Li L., Elliott J. F., Mosmann T. R. IL-10 inhibits cytokine production, vascular leakage, and swelling during T helper 1 cell-induced delayed-type hypersensitivity. J Immunol. 1994 Nov 1;153(9):3967–3978. [PubMed] [Google Scholar]
  19. 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]
  20. Mihara M., Ikuta M., Koishihara Y., Ohsugi Y. Interleukin 6 inhibits delayed-type hypersensitivity and the development of adjuvant arthritis. Eur J Immunol. 1991 Oct;21(10):2327–2331. doi: 10.1002/eji.1830211006. [DOI] [PubMed] [Google Scholar]
  21. Mody C. H., Lipscomb M. F., Street N. E., Toews G. B. Depletion of CD4+ (L3T4+) lymphocytes in vivo impairs murine host defense to Cryptococcus neoformans. J Immunol. 1990 Feb 15;144(4):1472–1477. [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Murphy J. W., Mosley R. L., Cherniak R., Reyes G. H., Kozel T. R., Reiss E. Serological, electrophoretic, and biological properties of Cryptococcus neoformans antigens. Infect Immun. 1988 Feb;56(2):424–431. doi: 10.1128/iai.56.2.424-431.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Pearlman E., Kazura J. W., Hazlett F. E., Jr, Boom W. H. Modulation of murine cytokine responses to mycobacterial antigens by helminth-induced T helper 2 cell responses. J Immunol. 1993 Nov 1;151(9):4857–4864. [PubMed] [Google Scholar]
  27. Piguet P. F., Grau G. E., Hauser C., Vassalli P. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med. 1991 Mar 1;173(3):673–679. doi: 10.1084/jem.173.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rivas J. M., Ullrich S. E. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. J Immunol. 1992 Dec 15;149(12):3865–3871. [PubMed] [Google Scholar]
  29. Rosenstein M., Ettinghausen S. E., Rosenberg S. A. Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol. 1986 Sep 1;137(5):1735–1742. [PubMed] [Google Scholar]
  30. Salkowski C. A., Balish E. A monoclonal antibody to gamma interferon blocks augmentation of natural killer cell activity induced during systemic cryptococcosis. Infect Immun. 1991 Feb;59(2):486–493. doi: 10.1128/iai.59.2.486-493.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sayers T. J., Wiltrout T. A., Bull C. A., Denn A. C., 3rd, Pilaro A. M., Lokesh B. Effect of cytokines on polymorphonuclear neutrophil infiltration in the mouse. Prostaglandin- and leukotriene-independent induction of infiltration by IL-1 and tumor necrosis factor. J Immunol. 1988 Sep 1;141(5):1670–1677. [PubMed] [Google Scholar]

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