Pneumocystis carinii Pneumonia in scid/scid Mice

Shultz, Leonard D.; Schweitzer, Peter A.; Hall, Elaine J.; Sundberg, John P.; Taylor, Suzanne; Walzer, Peter D.

doi:10.1007/978-3-642-74974-2_29

Cited by 32 publications

(22 citation statements)

References 10 publications

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“…Besides IGRP 206 -214 and INS-B [15][16][17][18][19][20][21][22][23] , which are targeted by 8.3 and G9C8, respectively (10,11), no other natural peptide targets for islet-infiltrating CD8 ϩ T cells in NOD mice have been identified to date. Three other candidate peptides of potential relevance have previously been described (40,41).…”

Section: Discussionmentioning

confidence: 99%

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Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Takaki

Lieberman

Holl

et al. 2004

The Journal of Immunology

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The NOD mouse is a model for autoimmune type 1 diabetes in humans. CD8+ T cells are essential for the destruction of the insulin-producing pancreatic β cells characterizing this disease. AI4 is a pathogenic CD8+ T cell clone, isolated from the islets of a 5-wk-old female NOD mouse, which is capable of mediating overt diabetes in the absence of CD4+ T cell help. Recent studies using MHC-congenic NOD mice revealed marked promiscuity of the AI4 TCR, as the selection of this clonotype can be influenced by multiple MHC molecules, including some class II variants. The present work was designed, in part, to determine whether similar promiscuity also characterizes the effector function of mature AI4 CTL. Using splenocyte and bone marrow disease transfer models and in vitro islet-killing assays, we report that efficient recognition and destruction of β cells by AI4 requires the β cells to simultaneously express both H-2Db and H-2Kd class I MHC molecules. The ability of the AI4 TCR to interact with both H-2Db and H-2Kd was confirmed using recombinant peptide libraries. This approach also allowed us to define a mimotope peptide recognized by AI4 in an H-2Db-restricted manner. Using ELISPOT and mimotope/H-2Db tetramer analyses, we demonstrate for the first time that AI4 represents a readily detectable T cell population in the islet infiltrates of prediabetic NOD mice. Our identification of a ligand for AI4-like T cells will facilitate further characterization and manipulation of this pathogenic and promiscuous T cell population.

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Section: Discussionmentioning

confidence: 99%

“…All mice are maintained under specific pathogenfree conditions and used in accordance with institutional guidelines for animal welfare. All scid mice receive a sulfamethoxazole-trimethoprim mixture in their drinking water on alternate weeks to prevent infection by Pneumocystis carinii (19).…”

Section: Micementioning

confidence: 99%

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Takaki

Lieberman

Holl

et al. 2004

The Journal of Immunology

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“…The extent (cyst density) and kinetics of infectivity by Pc and the time of morbidity caused by spontaneously acquired Pc pneumonia (PCP) in these mice are nearly identical to those described in that previous study. In brief, these mice have carried a stable and endemic Pc infection for more than 4 yr, developed plateau levels of organisms in -2 mo, lived an average of 5 mo, and were selected at random for inclusion in these studies.…”

Section: Methodsmentioning

confidence: 99%

“…Pneumocystis carini (Pc)' is the major diagnosed cause ofmorbidity in patients with AIDS (1), and has recently been reported to cause morbid pulmonary disease in mice homozygous for the recessive mutant gene scid (2)(3)(4). Scid mice are essentially devoid offunctional T or B lymphocytes and both primary and secondary lymphoid tissues are rudimentary (5)(6).…”

Section: Introductionmentioning

confidence: 99%

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

Roths¹,

Sidman²

1992

J. Clin. Invest.

150

131

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The opportunistic pathogen Pneumocystis carini (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. Invest. 1992.90:673-678.)

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Frequency and histological appearance of adenomas in multiple intestinal neoplasia mice are unaffected by severe combined immunodeficiency (scid) mutation

1996

Self Cite

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Well-characterized murine mutations are powerful analytical tools for the genetic analysis of tumorigenesis. We crossed the multiple intestinal neoplasia (Min) allele of adenomatous polyposis coli (Apc), which produces a profound pre-disposition to intestinal neoplasia, with the severe combined immunodeficiency (scid) mutation, which causes defective double-strand DNA repair and severe immunodeficiency, on the common C57BL/6) genetic background to assay for any combined effect on intestinal tumorigenesis. Several phenotypic traits were exacerbated in an apparently additive manner in the double mutant mice, including reduced immunoglobulin levels, reduced body weight and increased morbidity. However, quantitation and histological evaluation of polyp phenotype indicated that these mutations did not interact to affect either polyp frequency or progression. Thus, neither genome instability nor lack of immunosurveillance conferred by scid contributes to intestinal polyps in this model. o 1996 WiZey-Liss, Inc.Colorectal carcinoma is a genetically complex disease, influenced by environmental factors, heritable pre-disposing genes and somatic genetic mutations. Of these factors, somatic genetic mutations have been most extensively characterized, including inactivation of several tumor suppressor loci (Fearon and Vogelstein, 1990;Steele, 1993). One frequently mutated gene is adenomatous polyposis coli (Apc, mouse chromosome 18), which has been implicated as an initiating event in colonic epithelium transformation (Levy et al., 1994;Luongo et al., 1994). APC protein is physically associated with f3-catenin, suggesting that the loss of APC function may transform cells through cell adhesion or contact-mediated growth inhibitory pathways (Rubinfeld et al., 1993). Animal models for investigating the role of Apc in polyp initiation and carcinoma progression have been developed, including the multiple intestinal neoplasia (Min) mutation of mouse (Moser et al., 1990), which results from a non-sense mutation in the Apc gene (Su et al., 1992). ApcMip2 confers a phenotype of susceptibility to intestinal tumors that is dominantly inherited and 100% penetrant on the C57BLlJ (B6) background. Generation of a null allele of Apc by gene replacement technology has confirmed the Min phenotype (Fodde et aL, 1994).Genetic lesions that occur within tumor cells leading to cellular transformation are well documented, but much less is known about potential host genes that modify the frequency and phenotype of transforming mutations. The Min mutation has proven useful for investigating other genetic influences on adenoma incidence and phenotype. Tumor incidence in Min mice is highly dependent on genetic background, and a major modifier of Min has been mapped and a candidate gene identified (Dietrich et al., 1993;MacPhee et aL, 1995). Also, both pharmacological and genetic influences on DNA methylation have been shown to affect tumor incidence in Min mice (Laird et al., 1995). In contrast, dominant transforming genes (KrasVa1112 and p53A1a143) exp...

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Pneumocystis carinii Pneumonia in scid/scid Mice

Cited by 32 publications

References 10 publications

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

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

Frequency and histological appearance of adenomas in multiple intestinal neoplasia mice are unaffected by severe combined immunodeficiency (scid) mutation

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