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J Clin Invest. Aug 1992; 90(2): 673–678.
PMCID: PMC443150

Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice.


The opportunistic pathogen Pneumocystis carinii (Pc) is considered to be the leading cause of morbidity in patients with AIDS. It is important, therefore, to determine the immunological mechanisms of resistance to Pc. We have taken advantage of the lack of both T and B lymphocytes in severe combined immunodeficiency (scid) mice to determine the critical factors in resistance to spontaneously acquired Pc pneumonia. Using adoptive transfer of unfractionated or fractionated lymphocyte subsets or hyperimmune serum from congenic normal donors, we have demonstrated that effective immunity to Pc results from the action of CD4+ but not CD8+ T cells (in the absence of antibody) or from humoral immunity (in the absence of T cells). However, responses of CD4+ T cells (but not antibody) to already well-established burdens of Pc are often accompanied by a fatal hyperinflammatory reaction. The activity of CD4+ T cells against Pc thus illustrates a broadly applicable principle that T cell immunity represents a critical balance between consequences beneficial and harmful to the host.

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  • Mills J. Pneumocystis carinii and Toxoplasma gondii infections in patients with AIDS. Rev Infect Dis. 1986 Nov-Dec;8(6):1001–1011. [PubMed]
  • Roths JB, Marshall JD, Allen RD, Carlson GA, Sidman CL. Spontaneous Pneumocystis carinii pneumonia in immunodeficient mutant scid mice. Natural history and pathobiology. Am J Pathol. 1990 May;136(5):1173–1186. [PMC free article] [PubMed]
  • Sundberg JP, Burnstein T, Shultz LD, Bedigian H. Identification of Pneumocystis carinii in immunodeficient mice. Lab Anim Sci. 1989 May;39(3):213–218. [PubMed]
  • Shultz LD, Schweitzer PA, Hall EJ, Sundberg JP, Taylor S, Walzer PD. Pneumocystis carinii pneumonia in scid/scid mice. Curr Top Microbiol Immunol. 1989;152:243–249. [PubMed]
  • Custer RP, Bosma GC, Bosma MJ. Severe combined immunodeficiency (SCID) in the mouse. Pathology, reconstitution, neoplasms. Am J Pathol. 1985 Sep;120(3):464–477. [PMC free article] [PubMed]
  • Bancroft GJ, Schreiber RD, Unanue ER. T cell-independent macrophage activation in scid mice. Curr Top Microbiol Immunol. 1989;152:235–242. [PubMed]
  • Czitrom AA, Edwards S, Phillips RA, Bosma MJ, Marrack P, Kappler JW. The function of antigen-presenting cells in mice with severe combined immunodeficiency. J Immunol. 1985 Apr;134(4):2276–2280. [PubMed]
  • Dorshkind K, Pollack SB, Bosma MJ, Phillips RA. Natural killer (NK) cells are present in mice with severe combined immunodeficiency (scid). J Immunol. 1985 Jun;134(6):3798–3801. [PubMed]
  • Lai WC, Bennett M, Pakes SP, Kumar V, Steutermann D, Owusu I, Mikhael A. Resistance to Mycoplasma pulmonis mediated by activated natural killer cells. J Infect Dis. 1990 Jun;161(6):1269–1275. [PubMed]
  • Garni-Wagner BA, Witte PL, Tutt MM, Kuziel WA, Tucker PW, Bennett M, Kumar V. Natural killer cells in the thymus. Studies in mice with severe combined immune deficiency. J Immunol. 1990 Feb 1;144(3):796–803. [PubMed]
  • Dorshkind K, Keller GM, Phillips RA, Miller RG, Bosma GC, O'Toole M, Bosma MJ. Functional status of cells from lymphoid and myeloid tissues in mice with severe combined immunodeficiency disease. J Immunol. 1984 Apr;132(4):1804–1808. [PubMed]
  • Gradus MS, Ivey MH. An improved method of isolating Pneumocystis carinii from infected rat lungs. J Parasitol. 1986 Oct;72(5):690–698. [PubMed]
  • Meuwissen JH, Tauber I, Leeuwenberg AD, Beckers PJ, Sieben M. Parasitologic and serologic observations of infection with Pneumocystis in humans. J Infect Dis. 1977 Jul;136(1):43–49. [PubMed]
  • Peglow SL, Smulian AG, Linke MJ, Pogue CL, Nurre S, Crisler J, Phair J, Gold JW, Armstrong D, Walzer PD. Serologic responses to Pneumocystis carinii antigens in health and disease. J Infect Dis. 1990 Feb;161(2):296–306. [PubMed]
  • Rao CP, Gelfand EW. Pneumocystis carinii pneumonitis in patients with hypogammaglobulinemia and intact T cell immunity. J Pediatr. 1983 Sep;103(3):410–412. [PubMed]
  • Walzer PD, Rutledge ME. Serum antibody responses to Pneumocystis carinii among different strains of normal and athymic mice. Infect Immun. 1982 Feb;35(2):620–626. [PMC free article] [PubMed]
  • Gigliotti F, Hughes WT. Passive immunoprophylaxis with specific monoclonal antibody confers partial protection against Pneumocystis carinii pneumonitis in animal models. J Clin Invest. 1988 Jun;81(6):1666–1668. [PMC free article] [PubMed]
  • Furuta T, Ueda K, Fujiwara K. Experimental Pneumocystis carinii infection in nude rats. Jpn J Exp Med. 1984 Apr;54(2):65–72. [PubMed]
  • Furuta T, Ueda K, Kyuwa S, Fujiwara K. Effect of T-cell transfer on Pneumocystis carinii infection in nude mice. Jpn J Exp Med. 1984 Apr;54(2):57–64. [PubMed]
  • Furuta T, Ueda K, Fujiwara K, Yamanouchi K. Cellular and humoral immune responses of mice subclinically infected with Pneumocystis carinii. Infect Immun. 1985 Feb;47(2):544–548. [PMC free article] [PubMed]
  • Goedert JJ, Biggar RJ, Melbye M, Mann DL, Wilson S, Gail MH, Grossman RJ, DiGioia RA, Sanchez WC, Weiss SH, et al. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus. JAMA. 1987 Jan 16;257(3):331–334. [PubMed]
  • Masur H, Ognibene FP, Yarchoan R, Shelhamer JH, Baird BF, Travis W, Suffredini AF, Deyton L, Kovacs JA, Falloon J, et al. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989 Aug 1;111(3):223–231. [PubMed]
  • Brunvand MW, Collins C, Livingston RB, Raghu G. Pneumocystis carinii pneumonia associated with profound lymphopenia and abnormal T-lymphocyte subset ratios during treatment for early-stage breast carcinoma. Cancer. 1991 May 1;67(9):2407–2409. [PubMed]
  • Shellito J, Suzara VV, Blumenfeld W, Beck JM, Steger HJ, Ermak TH. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest. 1990 May;85(5):1686–1693. [PMC free article] [PubMed]
  • Harmsen AG, Stankiewicz M. Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice. J Exp Med. 1990 Sep 1;172(3):937–945. [PMC free article] [PubMed]
  • Roifman CM, Hummel D, Martinez-Valdez H, Thorner P, Doherty PJ, Pan S, Cohen F, Cohen A. Depletion of CD8+ cells in human thymic medulla results in selective immune deficiency. J Exp Med. 1989 Dec 1;170(6):2177–2182. [PMC free article] [PubMed]
  • Masur H, Jones TC. The interaction in vitro of Pneumocystis carinii with macrophages and L-cells. J Exp Med. 1978 Jan 1;147(1):157–170. [PMC free article] [PubMed]
  • Magee DM, Williams DM, Wing EJ, Bleicker CA, Schachter J. Production of colony-stimulating factors during pneumonia caused by Chlamydia trachomatis. Infect Immun. 1991 Jul;59(7):2370–2375. [PMC free article] [PubMed]
  • Finkelman FD, Katona IM, Mosmann TR, Coffman RL. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988 Feb 15;140(4):1022–1027. [PubMed]
  • Jättelä M. Biologic activities and mechanisms of action of tumor necrosis factor-alpha/cachectin. Lab Invest. 1991 Jun;64(6):724–742. [PubMed]
  • Tamburrini E, De Luca A, Ventura G, Maiuro G, Siracusano A, Ortona E, Antinori A. Pneumocystis carinii stimulates in vitro production of tumor necrosis factor-alpha by human macrophages. Med Microbiol Immunol. 1991;180(1):15–20. [PubMed]
  • Krishnan VL, Meager A, Mitchell DM, Pinching AJ. Alveolar macrophages in AIDS patients: increased spontaneous tumour necrosis factor-alpha production in Pneumocystis carinii pneumonia. Clin Exp Immunol. 1990 May;80(2):156–160. [PMC free article] [PubMed]
  • Darling G, Fraker DL, Jensen JC, Gorschboth CM, Norton JA. Cachectic effects of recombinant human tumor necrosis factor in rats. Cancer Res. 1990 Jul 1;50(13):4008–4013. [PubMed]
  • Scuderi P, Sterling KE, Lam KS, Finley PR, Ryan KJ, Ray CG, Petersen E, Slymen DJ, Salmon SE. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet. 1986 Dec 13;2(8520):1364–1365. [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]
  • Ferro TJ, Johnson A, Everitt J, Malik AB. IL-2 induces pulmonary edema and vasoconstriction independent of circulating lymphocytes. J Immunol. 1989 Mar 15;142(6):1916–1921. [PubMed]
  • Syrjälä H, Lähdevirta J, Ruutu P, Jokipii L, Jokipii AM, Ruutu T. Acute phase response in Pneumocystis carinii pneumonia. Scand J Infect Dis. 1990;22(6):713–716. [PubMed]
  • Breel M, Van der Ende M, Sminia T, Kraal G. Subpopulations of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the mouse. Immunology. 1988 Apr;63(4):657–662. [PMC free article] [PubMed]
  • Amundson DE, Murray KM, Brodine S, Oldfield EC. High-dose corticosteroid therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. South Med J. 1989 Jun;82(6):711–718. [PubMed]

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