Genetic and immunological parameters governing <i>in vivo</i> susceptibility/resistance to retrovirally induced murine malignant histiocytosis

Panoskaltsis‐Mortari, Angela; Egeler, R. Maarten; Yaeger, Ted; Yoneji, S; Schmitz, Louise F.; Lilly, Frank; Nesbit, Mark E.; Blazar, Bruce R.

doi:10.1002/jlb.64.4.441

Cited by 4 publications

(5 citation statements)

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“…The importance of the T‐cell response in the elimination of tumors and the association of tumor progression with a poor or inhibited T‐cell response have been analyzed extensively (Fig. 3 j ) 19, 36, 37. Both SCID and nude mice, which are unable to generate mature T cells, exhibit high susceptibility to tumor development 38, 39, 40, 41, 42.…”

Section: Discussionmentioning

confidence: 99%

“…BXD mice have been used for genetic mapping of disease susceptibility13, 14 and for studying the development of the nervous system15, 16, 17 and alcohol abuse 6, 18. Several investigators have recognized the advantage of using these mice to identify both MHC‐related and non‐MHC‐related genetic loci that affect the shaping of the repertoire and the function of the immune system 7, 13, 19, 20, 21. Waters et al22 utilized these mice to show that the genetic restriction involved in KLH antigen‐specific proliferation maps to the mls gene on chromosome 1.…”

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confidence: 99%

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BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model

Grizzle

Mountz

Yang

et al. 2002

Intl Journal of Cancer

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To develop a better animal model for studying the effects of the host environment in neoplasia, we injected various genetically well-characterized H-2 d RI strains of BXD mice with syngeneic breast cancer cells (TS/A) and monitored the growth of tumors over time. There was a marked difference in the growth of the implanted breast cancer cells among the 14 BXD RI strains, with 4 patterns of tumor development being observed: in type I, the implanted tumor cells grew rapidly in the first 2 weeks, necrosis of the tumors was observed and metastases to the intestinal lymph nodes and pancreas was observed, causing death; in type II, the implanted tumor cells grew slowly and attained a size after day 50 that required killing the animal, with tumor necrosis being rare and metastases absent; in type III, the implanted tumor cells grew initially but underwent a slow decline after 4 weeks; and in type IV, the implanted tumor cells failed to Characterization of the effect of the host environment on the development and progression of tumors has proven difficult due, in part, to the lack of informative models. The immune surveillance system, which is thought to play a key role in determining susceptibility or resistance to tumor growth, shows considerable variation among individuals. Although immunodeficient nude and SCID mice are useful tools for the characterization of the role of the host environment in the development and progression of human-derived tumors, 1,2 the lack of an intact immune system in these mice results in an incomplete picture of the potential mechanisms involved and their relative contribution to tumor growth. Comparative analysis of implanted syngeneic TS/A tumor cells in C57BL/6 mice, which are resistant to implanted tumors, and DBA/2 mice, which are susceptible, is a good model for the dissection of the host immune response to tumors but is limited by the lack of response diversity. [3][4][5] The genetically well-characterized BXD RI strain of mice was derived by intercrossing F 2 mice derived from DBA/2 and C57BL/6 mice for more than 20 generations to fix homozygous loci. These strains exhibit a broad spectrum of traits, including diversity in the types and intensity of the immune responses. 6 -12 The availability of these mice therefore presented an opportunity to develop an alternative model to analyze the mechanisms that determine the immune response to tumor cells. BXD mice have been used for genetic mapping of disease susceptibility 13,14 and for studying the development of the nervous system 15-17 and alcohol abuse. 6,18 Several investigators have recognized the advantage of using these mice to identify both MHCrelated and non-MHC-related genetic loci that affect the shaping of the repertoire and the function of the immune system. 7,13,19 -21 Waters et al. 22 utilized these mice to show that the genetic restriction involved in KLH antigen-specific proliferation maps to the mls gene on chromosome 1. Scalzo et al. 20 showed that the resistance of mice to lethal infection by MCMV is associated ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model

Grizzle

Mountz

Yang

et al. 2002

Intl Journal of Cancer

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“…The remarkable cell type specificity of transformation and the characteristics of the resulting disease justified naming the pathogenic retrovirus ‘malignant histiocytosis sarcoma virus’ (MHSV). Evaluation of the genetic parameters important for disease susceptibility indicated that the resistance phenotype was linked with high probability to loci on mouse chromosome 13 (83). Interestingly, this area is homologous to human chromosome 5q35, which has been associated with human malignant histiocytosis as well as other proliferative diseases involving myeloid or histiocytic aspects (84, 85).…”

Section: Are Lch Cells Intrinsically Aberrant?mentioning

confidence: 99%

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Egeler

Halteren

Hogendoorn

et al. 2010

Immunological Reviews

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In its rare occurrence, Langerhans cell histiocytosis (LCH) is a dangerous but intriguing deviation of mononuclear phagocytes, especially dendritic cells (DCs). Clinically, the disease ranges from self-resolving or well manageable to severe and even fatal. LCH lesions in skin, bone, and other sites contain high numbers of cells with phenotypic features resembling LCs admixed with macrophages, T cells, eosinophils, and multinucleated giant cells. Here we review current progress in the LCH field based on two central questions: (i) are LCH cells intrinsically aberrant, and (ii) how does the lesion drive pathogenesis? We argue that LCH cells may originate from different sources, including epidermal LCs, tissue Langerin(+) DCs, or mononuclear phagocyte precursors. Current and prospective in vitro and in vivo models are discussed. Finally, we discuss recent insights into plasticity of T-helper cell subsets in light of the lesion microenvironment. LCH continues to provide urgent clinical questions thereby inspiring innovative DC lineage research.

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“…The clinical and pathological symptoms observed in MHSVinfected mice show resemblance to those observed in human disease involving malignant histiocytic cells, thus suggesting that this is a putative model for the disease [6,9]. This is reinforced by the finding that resistance to MHSV infection is genetically linked to a chromosome region homologous to human 5q35 [10]. This region has been associated with human malignant histiocytosis (MH) [11], as well as with other neoplastic hematopoietic diseases with myeloid and/or histiocytic aspects, including acute myeloid leukemia (AML) and anaplastic large cell lymphoma (ALCL), in which malignant lymphoid cells have a histiocyte-like appearance [12,13].…”

Section: Introductionmentioning

confidence: 93%

“…Animals were specific pathogen-free and were kept with free access to food and water. Both DDD and BALB/c mice are susceptible for disease development due to MHSV-infection [5,10]. Mice were killed using CO 2 suffocation.…”

Section: Micementioning

confidence: 99%

Heterogeneity in a mouse model of histiocytosis: transformation of Langerin+ dendritic cells, macrophages, and precursors

Leenen

Bechan

Melis

et al. 2010

Journal of Leukocyte Biology

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Neoplastic diseases of macrophages (M phi) and dendritic cells (DC), collectively called histiocytoses, are relatively rare. The etiology of most forms of histiocytosis is poorly understood, and the development of animal models is crucial for further research in this field. Previously, an animal model for malignant histiocytosis (MH), involving transformed histiocytic cells, has been generated by infecting mice with malignant histiocytosis sarcoma virus (MHSV). However, increased insight into the heterogeneity of M phi and DC, and the associated reappraisal of human proliferative diseases involving these cells inspired us to re-evaluate the mouse model. We analyzed spleen, bone marrow, and lymph nodes of susceptible mice at various time points after infection. From day 11 onwards, a heterogeneous population of cells, consisting of CD8 alpha(+) Langerin(+) DC, ER-MP58(+) CD11b(+) myeloid precursor cells, CD169(+) metallophilic M phi, and CD71(hi) erythroblasts, was affected by viral transformation. In different mice, these subsets expanded at different rates in different organs, causing a variable disease profile in terminal stages. Cell lines, which were generated from MHSV-transformed tumors, showed a DC-like morphology and phenotype, and appeared to be arrested in different stages of maturation. Upon injection into healthy mice, different preferential homing patterns were observed for the various cell lines, and the cells acquired distinct phenotypes depending on the organ of homing. This indicates that these transformed cells adapt to their microenvironment by switching between precursor, DC/Langerhans cell, and M phi phenotypes. Our results demonstrate that the MHSV model represents a heterogeneous neoplastic disease with characteristics of M phi/DC sarcomas.

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Genetic and immunological parameters governing in vivo susceptibility/resistance to retrovirally induced murine malignant histiocytosis

Cited by 4 publications

References 50 publications

BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model

BXD recombinant inbred mice represent a novel T cell–mediated immune response tumor model

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Heterogeneity in a mouse model of histiocytosis: transformation of Langerin+ dendritic cells, macrophages, and precursors

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