Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

Theus, Sue A.; Andrews, Ryan P.; Steele, Paul; Walzer, Peter D.

doi:10.1172/jci117960

Cited by 66 publications

(61 citation statements)

References 31 publications

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“…50 Similar mechanisms may be at work in fungal infections, specific CD4 cells being essential to control Candida and Pneumo- cystis in in vivo models. 51,52 Other opportunistic agents most frequently responsible for symptomatic infections, accompanying disappearance of the CD4 defence, include viruses such as EBV and CMV. In this case, the immune defect likely resides in the loss of CD4 helper cells that fail to activate and to expand virus-specific cytotoxic CD8 lymphocytes.…”

Section: Antigen-specific Cd4 Lymphocytes and Their Use In A New Combmentioning

confidence: 99%

Genetically modified immunocompetent cells in HIV infection

Palù

Pira²,

Gennari

et al. 2001

Gene Ther

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Even in the era of highly active antiretroviral therapy (HAART), gene therapy (GT) can remain a promising approach for suppressing HIV infection, especially if complemented with other forms of pharmacological and immunological intervention. A large number of vectors and targets have been studied. Here we discuss the potential of genetically treated, antigen-specific immunocompetent cells for adoptive autologous immunotherapy of HIV infection. Cellu-

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Section: Antigen-specific Cd4 Lymphocytes and Their Use In A New Combmentioning

confidence: 99%

Genetically modified immunocompetent cells in HIV infection

Palù

Pira²,

Gennari

et al. 2001

Gene Ther

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“…All rats used in this study were exposed to Pneumocystis by being housed with CS-treated rats with active Pneumocystis pneumonia. Pneumocystis pneumonia was induced in rats by subcutaneous injections of methylprednisolone acetate (4.0 mg/0.2 ml/week; Depo-Medrol; Pharmacia and Upjohn Co., Kalamazoo, Mich.), as described previously (35). All animals were handled according to institutionally recommended guidelines.…”

Section: Animalsmentioning

confidence: 99%

“…The total cell count per spleen is reported in Lung processing and Pneumocystis carinii enumeration. The right lung from each animal was used for quantitation of Pneumocystis cysts and nuclei as previously described (16,35,36). Lungs were minced in 10.0 ml of phosphatebuffered saline (PBS), homogenized in a Stomacher 80 (Tekmar, Inc., Gehanna, Ohio), and filtered through gauze.…”

Section: Animalsmentioning

confidence: 99%

“…A portion of the left lung lobe was excised and immersed in 10% buffered formalin. Lung histological sections were stained with hematoxylin-eosin (HϩE) and Grocott-Gomori methenamine-silver nitrate (GMS) as described elsewhere (35).…”

Section: Animalsmentioning

confidence: 99%

“…Statistical analyses were performed by using Graphpad Instat and Prism (San Diego, Calif.) software. Data were compared by analysis of variance followed by the Student-Neuman-Keuls test for multiple comparisons (35). A P value Ͻ 0.05 was considered significant.…”

Section: Animalsmentioning

confidence: 99%

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New Rat Model ofPneumocystisPneumonia Induced by Anti-CD4⁺T-Lymphocyte Antibodies

Thullen

Ashbaugh²,

Daly³

et al. 2003

Infect Immun

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The CD4؉ T lymphocyte plays a central role in host defense against Pneumocystis pneumonia but has received only limited attention in rats. CD4؉ T-cell-depleting (OX-38) and nondepleting (W3/25) monoclonal antibodies, which recognize an identical or adjacent epitope, were administered for up to 14 weeks to Lewis rats that had been exposed to Pneumocystis. While OX-38 produced a greater decrease in circulating CD4؉ cells than W3/25, both antibody treatments resulted in similar effects on the health of the rats and the levels of Pneumocystis pneumonia, which were milder than those found with corticosteroids. W3/25 also did not enhance the severity of Pneumocystis pneumonia achieved with corticosteroids alone. We conclude that CD4 ؉ cell function is more important than CD4؉ cell number in host defense against Pneumocystis in the rat and that this new model permits study of opportunistic infections in the rat without the confounding effects of corticosteroids.Pneumocystis is an extracellular fungus of low virulence that causes pneumonia in immunocompromised individuals, such as human immunodeficiency virus-positive patients and cancer and organ transplant patients. Various immunodeficient and immunosuppressed rat and mouse models have been used to study the interaction between Pneumocystis and host (9,11,31,32). The corticosteroid (CS)-treated rat is the original animal model used to study Pneumocystis pneumonia and is the source of most available information on the epidemiology, immunopathogenesis, diagnosis, and therapy of the disease (3, 9). However, this model is limited by the broad immunosuppressive effects of steroids on the immune system, including lymphocyte depletion and impairment of function, reduced leukocyte chemotaxis and phagocytosis, and deficient antibody (Ab) production (38).Clinical and experimental studies have shown that CD4 ϩ T lymphocytes play a central role in host defenses against Pneumocystis (14,25,29,37). Pneumocystis pneumonia can be induced in mice exposed to the organism by the administration of GK1.5, a rat immunoglobulin G2b (IgG2b) monoclonal antibody (MAb) specific for CD4 ϩ cells (31). This model has proven to be popular because it circumvents the need for CS immunosuppression; however, no such model exists in rats. Given the increasing evidence of the genetic diversity and host specificity of Pneumocystis (6, 33), it cannot be assumed that the results obtained in one animal species can be applied to another. The development of a CD4 ϩ depletion model in the rat would be important in studying the role of CD4 ϩ T cells in the rat.MAbs have been produced to rat CD4 ϩ cells, and their properties have been analyzed by in vitro or short-term in vivo studies (2,5,26,39). These Abs are of two general types: depleting Abs, which trigger cell lysis; and nondepleting Abs, which cause downregulation of CD4 antigen expression resulting in inadequate T-cell receptor (TCR)-antigen-major histocompatibility complex class II interaction (34). These Abs have been used in a variety of autoimmune or ...

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Pneumocystis carinii Pneumonia Masquerading as Tuberculosis

Sarkar

Dubé²,

Jones³

et al. 1997

Arch Intern Med

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Recent laboratory studies indicate that genetic diversity exists in human strains of Pneumocystis carinii. Structural and functional variability in infecting strains could result in differences in host-parasite interactions and the natural history of P carinii pneumonia. We report 5 unusual cases in which the clinical presentation mimicked tuberculosis. All patients were cared for at a university-based public hospital clinic in Los Angeles, Calif, during a 2-year period. These patients were chronically ill, had lost weight, and each had cavities or cystic spaces as the primary radiographic findings. None were receiving aerosol pentamidine and only one had a history of smoking. Four patients were initially treated for tuberculosis and the fifth for disseminated Mycobacterium avium complex. Pneumocystis carinii was the only pathogen identified in each case. The unusual clinical presentations delayed the diagnosis of P carinii in all 5 cases. Practitioners must be aware of the variable presentations of P carinii pneumonia.

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Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

Cited by 66 publications

References 31 publications

Genetically modified immunocompetent cells in HIV infection

Genetically modified immunocompetent cells in HIV infection

New Rat Model ofPneumocystisPneumonia Induced by Anti-CD4⁺T-Lymphocyte Antibodies

Pneumocystis carinii Pneumonia Masquerading as Tuberculosis

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Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

Cited by 66 publications

References 31 publications

Genetically modified immunocompetent cells in HIV infection

Genetically modified immunocompetent cells in HIV infection

New Rat Model ofPneumocystisPneumonia Induced by Anti-CD4+T-Lymphocyte Antibodies

Pneumocystis carinii Pneumonia Masquerading as Tuberculosis

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Product

Resources

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New Rat Model ofPneumocystisPneumonia Induced by Anti-CD4⁺T-Lymphocyte Antibodies