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Proc Natl Acad Sci U S A. 1991 Aug 15; 88(16): 7011–7015.
PMCID: PMC52223

Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis.

Abstract

The expression of interleukin (IL) 2, IL-4, IL-10, and interferon gamma (IFN-gamma) by lymphocyte subsets was examined during infection of resistant C57BL/6 and susceptible BALB/c mice with the protozoan parasite Leishmania major. CD4+ and CD8+ T lymphocytes and B lymphocytes were isolated from the lymph nodes draining infectious lesions, and their RNA was examined for lymphokine transcripts. Distinct patterns of CD4+ cell cytokine expression were apparent: C57BL/6 CD4+ cells contained IFN-gamma and IL-2 mRNA, whereas BALB/c CD4+ cells expressed IL-4 and IL-10 message. CD8+ cells contributed little lymphokine expression during disease, but B cells were a major source of IL-2 mRNA in both strains of mice. BALB/c mice made resistant by treatment with anti-CD4 antibody at the time of infection repopulated lymph nodes with CD4+ cells that expressed IL-2 and IFN-gamma. Protective treatment with anti-IL-4 antibody in vivo also resulted in the appearance of CD4+ cells with increased IFN-gamma and diminished IL-4 and IL-10 expression. These data establish CD4+ cells as the primary source of IFN-gamma in healing mice and of IL-4 and IL-10 during progressive infection and confirm that the spectral extremes of this disease are characterized by the presence of CD4+ cells expressing Th1 or Th2 phenotypes in vivo.

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  • Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. [PMC free article] [PubMed]
  • Belosevic M, Finbloom DS, Van Der Meide PH, Slayter MV, Nacy CA. Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J Immunol. 1989 Jul 1;143(1):266–274. [PubMed]
  • Liew FY, Millott S, Li Y, Lelchuk R, Chan WL, Ziltener H. Macrophage activation by interferon-gamma from host-protective T cells is inhibited by interleukin (IL)3 and IL4 produced by disease-promoting T cells in leishmaniasis. Eur J Immunol. 1989 Jul;19(7):1227–1232. [PubMed]
  • Lehn M, Weiser WY, Engelhorn S, Gillis S, Remold HG. IL-4 inhibits H2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma. J Immunol. 1989 Nov 1;143(9):3020–3024. [PubMed]
  • Peleman R, Wu J, Fargeas C, Delespesse G. Recombinant interleukin 4 suppresses the production of interferon gamma by human mononuclear cells. J Exp Med. 1989 Nov 1;170(5):1751–1756. [PMC free article] [PubMed]
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. 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]
  • Müller I, Pedrazzini T, Farrell JP, Louis J. T-cell responses and immunity to experimental infection with leishmania major. Annu Rev Immunol. 1989;7:561–578. [PubMed]
  • Scott P, Natovitz P, Coffman RL, Pearce E, Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. [PMC free article] [PubMed]
  • Scott P, Caspar P, Sher A. Protection against Leishmania major in BALB/c mice by adoptive transfer of a T cell clone recognizing a low molecular weight antigen released by promastigotes. J Immunol. 1990 Feb 1;144(3):1075–1079. [PubMed]
  • Gajewski TF, Joyce J, Fitch FW. Antiproliferative effect of IFN-gamma in immune regulation. III. Differential selection of TH1 and TH2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-gamma. J Immunol. 1989 Jul 1;143(1):15–22. [PubMed]
  • Gajewski TF, Pinnas M, Wong T, Fitch FW. Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J Immunol. 1991 Mar 15;146(6):1750–1758. [PubMed]
  • Lohoff M, Sommer F, Solbach W, Röllinghoff M. Coexistence of antigen-specific TH1 and TH2 cells in genetically susceptible BALB/c mice infected with Leishmania major. Immunobiology. 1989 Oct;179(4-5):412–421. [PubMed]
  • Farrell JP, Muller I, Louis JA. A role for Lyt-2+ T cells in resistance to cutaneous leishmaniasis in immunized mice. J Immunol. 1989 Mar 15;142(6):2052–2056. [PubMed]
  • Hill JO, Awwad M, North RJ. Elimination of CD4+ suppressor T cells from susceptible BALB/c mice releases CD8+ T lymphocytes to mediate protective immunity against Leishmania. J Exp Med. 1989 May 1;169(5):1819–1827. [PMC free article] [PubMed]
  • Titus RG, Milon G, Marchal G, Vassalli P, Cerottini JC, Louis JA. Involvement of specific Lyt-2+ T cells in the immunological control of experimentally induced murine cutaneous leishmaniasis. Eur J Immunol. 1987 Oct;17(10):1429–1433. [PubMed]
  • Gessner A, Moskophidis D, Lehmann-Grube F. Enumeration of single IFN-gamma-producing cells in mice during viral and bacterial infection. J Immunol. 1989 Feb 15;142(4):1293–1298. [PubMed]
  • Fong TA, Mosmann TR. Alloreactive murine CD8+ T cell clones secrete the Th1 pattern of cytokines. J Immunol. 1990 Mar 1;144(5):1744–1752. [PubMed]
  • Bancroft GJ, Sheehan KC, Schreiber RD, Unanue ER. Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice. J Immunol. 1989 Jul 1;143(1):127–130. [PubMed]
  • Sadick MD, Heinzel FP, Holaday BJ, Pu RT, Dawkins RS, Locksley RM. Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990 Jan 1;171(1):115–127. [PMC free article] [PubMed]
  • Titus RG, Ceredig R, Cerottini JC, Louis JA. Therapeutic effect of anti-L3T4 monoclonal antibody GK1.5 on cutaneous leishmaniasis in genetically-susceptible BALB/c mice. J Immunol. 1985 Sep;135(3):2108–2114. [PubMed]
  • Littman DR, Gettner SN. Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene. Nature. 325(6103):453–455. [PubMed]
  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. [PubMed]
  • Sadick MD, Heinzel FP, Shigekane VM, Fisher WL, Locksley RM. Cellular and humoral immunity to Leishmania major in genetically susceptible mice after in vivo depletion of L3T4+ T cells. J Immunol. 1987 Aug 15;139(4):1303–1309. [PubMed]
  • Budd RC, Cerottini JC, MacDonald HR. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [PubMed]
  • Guagliardi LE, Koppelman B, Blum JS, Marks MS, Cresswell P, Brodsky FM. Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature. 1990 Jan 11;343(6254):133–139. [PubMed]
  • Brunt LM, Portnoy DA, Unanue ER. Presentation of Listeria monocytogenes to CD8+ T cells requires secretion of hemolysin and intracellular bacterial growth. J Immunol. 1990 Dec 1;145(11):3540–3546. [PubMed]
  • Fiorentino DF, Bond MW, Mosmann TR. 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. [PMC free article] [PubMed]
  • Carvalho EM, Badaró R, Reed SG, Jones TC, Johnson WD., Jr Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis. J Clin Invest. 1985 Dec;76(6):2066–2069. [PMC free article] [PubMed]
  • Zwingenberger K, Harms G, Pedrosa C, Omena S, Sandkamp B, Neifer S. Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production. Clin Immunol Immunopathol. 1990 Nov;57(2):242–249. [PubMed]
  • Taira S, Matsui M, Hayakawa K, Yokoyama T, Nariuchi H. Interleukin secretion by B cell lines and splenic B cells stimulated with calcium ionophore and phorbol ester. J Immunol. 1987 Nov 1;139(9):2957–2964. [PubMed]
  • Scott P, Natovitz P, Sher A. B lymphocytes are required for the generation of T cells that mediate healing of cutaneous leishmaniasis. J Immunol. 1986 Aug 1;137(3):1017–1021. [PubMed]
  • Ben-Sasson SZ, Le Gros G, Conrad DH, Finkelman FD, Paul WE. IL-4 production by T cells from naive donors. IL-2 is required for IL-4 production. J Immunol. 1990 Aug 15;145(4):1127–1136. [PubMed]
  • Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990 Sep 1;172(3):921–929. [PMC free article] [PubMed]
  • Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990 Dec 1;145(11):3796–3806. [PubMed]

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