Phenotype and Natural Killer Cell Sensitivity of a Radiation‐Induced Acute T‐Cell Leukaemia (Roser Leukaemia) in PVG Rats

Nestvold, Janne; Stokland, Ann-Elin Meling; Naper, Christian; Rolstad, Bent

doi:10.1111/j.0300-9475.2004.01436.x

Cited by 11 publications

(18 citation statements)

References 25 publications

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“…At the terminal phase such leukaemic infiltration occupied 16% of the total interstitial volume (Jahnukainen et al, 1994). Roser's rat leukaemic cells express surface markers characteristic of immature T-lymphoblasts (Nestvold et al, 2004). All of these features suggest that Roser's rat leukaemia may provide a valuable model of the testicular infiltration associated with childhood acute lymphoblastic leukaemia (ALL).…”

Section: Discussionmentioning

confidence: 99%

Immunomagnetic separation of normal rat testicular cells from Roser’s T‐cell leukaemia cells is ineffective

et al. 2009

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Elimination of contaminating malignant cells is crucial to avoiding cancer relapse in association with transplantation of autologous spermatogonial stem cells. In the clinical setting, there is presently no effective procedure for separating testicular cells from cancer cells. Here, CD4, a selective surface marker for Roser's rat leukaemic T-cells, was utilized to eliminate cancer cells from testicular cell samples from leukaemic piebald variegated (PVG) rats by magnetic-activated cell sorting (MACS). All animals receiving MACS-selected testicular cells died within 14-15 days. Only one-third of the contaminating leukaemic cells could be removed from testicular samples. An increase in antibody concentration enhanced the proportion of leukaemic cells removed from 27 to 49%. Variations in the cell size and expression of surface antigens on testicular leukaemic cells were the major obstacles to purification based on this marker. It is concluded that MACS does not prevent transmission of leukaemia to syngenic PVG rats when cells from leukaemic testes are used for testicular cell transplantation.

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Section: Discussionmentioning

confidence: 99%

Immunomagnetic separation of normal rat testicular cells from Roser’s T‐cell leukaemia cells is ineffective

et al. 2009

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“…Primary cells were enriched for mononuclear cells by centrifugation on Lymphoprep before use. The following cell lines were used: cc531s (rat colon carcinoma), RBL-2H3 (rat mucosal mast cell), RNK-16 (rat NK-cell leukemia), R2 (rat macrophage), YB2/0 (rat B-cell myeloma), Roser leukemia (RL; rat T-cell leukemia, [32], CHO cells, and 293T (human kidney fibroblast). Cell lines were maintained in complete RPMI (RPMI 1640 supplemented with 25 mM HEPES, 10% heat-inactivated FBS, 1 mM MEM sodium pyruvate, 5 Â 10 À5 M 2-mercaptoethanol, and antibiotics).…”

Section: Flow Cytometry Mab and Cellsmentioning

confidence: 99%

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

et al. 2009

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A major subset of non-alloreactive NK cells in PVG strain rats is generally low in Ly49 receptors, but expresses the rat NKR-P1B PVG receptor (previously termed NKR-P1C). The NKR-P1B 1 NK subset is inhibited by a non-polymorphic target cell ligand, which we have shown here to be a C-type lectin-related molecule (Clr). Clr11 ligates two divergent NKR-P1B alleles as judged by an NFAT-driven reporter assay, and inhibits NK-cell cytotoxicity of NKR-P1B 1 NK cells. Clr11 also interacts with the prototypic NKR-P1A receptor and exerts a stimulatory influence on NK lysis. NKR-P1A and B are encoded by adjacent genes in the proximal part of the NK gene complex and show close sequence homology in their extracellular region. They diverge from another pair, NKR-P1F and -G, which is encoded by a second, distal Nkrp1 gene cluster. NKR-P1F and -G bind an overlapping panel of Clr ligands, but not Clr11. Rat Clr molecules appear to be constitutively expressed by hematopoietic cells; expression in tumor cell lines is more variable. The data show the existence of two phylogenetic groups of NKR-P1 molecules, which demonstrate conservation of ligand-binding properties independent of signaling function.Key words: Cytotoxicity . NK cells . Receptor . Rodent Introduction NK cells express several families of killer cell lectin-like receptors (KLR). These are type II transmembrane proteins encoded by the NK gene complex (NKC), which is located on chromosome 4 in the rat [1,2]. The NKR-P1 molecules (KLRB or CD161) were among the first KLR to be characterized, but their function long remained elusive [3][4][5]. Although the NKR-P1 family has expanded to include both activating and inhibitory members in rodents, it consists of only one member in several other mammalian species, including in human [6]. The nature of their ligands has been controversial [7,8], but it has recently been shown that members of another KLR-related receptor family, the C-type lectin-related (Clr) molecules [9], also termed C-type lectin 2D (CLEC2D), can act as ligands for certain NKR-P1 molecules [10,11]. The Clr gene family also shows considerable expansion in rodents and the Clr genes are interspersed with the Nkrp1 genes in the proximal (centromeric) part of the NKC. A recent analysis concluded that there are 11 Clr/Clec2d genes in the rat BN strain genome, which were numbered consecutively from proximal to distal. One of these (Clr8) is most likely only a gene fragment, which could have been excluded, but we will nevertheless adhere to the Clr numbering suggested by Hao et al. [6].In the mouse, the inhibitory NKR-P1B and -D receptors both bind Clrb (also termed Ocil). Clrb is constitutively expressed by hematopoietic cells and inhibits cytolytic activity of NKR-P1B/ D-expressing NK cells [10,11]. The activating NKR-P1F receptor has been shown to bind another Clr molecule, Clrg, by the use of a reporter assay and soluble recombinant proteins [11] functional consequence of this interaction remains obscure. In human, the NKR-P1A receptor binds a Clr orthologue term...

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“…This leukemia infiltrates immature testicular tissue (Jahnukainen et al 1993) and the leukemic cells express the surface markers characteristic of immature T-lymphoblasts (Nestvold et al 2004), properties that closely resemble those of human ALL. Following injection of more than 20 leukemic T-cells into a syngeneic rat, uninterrupted progression of leukemia occurs during a period of 14-19 days.…”

Section: Introductionmentioning

confidence: 99%

Decontamination of leukemic cells and enrichment of germ cells from testicular samples from rats with Roser’s T-cell leukemia by flow cytometric sorting

Hou¹,

Andersson²,

Zheng³

et al. 2007

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Testicular germ cell transplantation is a novel strategy for preservation of fertility in prepubertal cancer patients, but the risk of reseeding tumor cells into cured patients presently limits clinical application of this approach. To date, no systematic evaluation of the limitations of surface marker-based decontamination of testicular samples with acute lymphoblastic leukemia has been performed. Here, surface markers for leukemic (CD4 and major histocompatibility complex class I) and germ cells (epithelia cell adhesion molecule) in testicular samples infiltrated with Roser's T-cell leukemia were identified. These markers were then used to delete leukemic cells and/or select for germ cells by flow cytometry (FACS). The resulting cell populations were analyzed by FACS, immunocytochemistry, or evaluation of leukemia transmission in syngeneic piebald variegated rats. Simple positive selection of germ cells or deletion of leukemic cells using specific surface markers was unable to effectively decontaminate testicular samples. The poor specificity of spermatogonial surface markers and aggregation of germ and leukemic cells limited the positive selection of germ cells, while immunophenotypic variation among lymphoblastic leukemia cells prevented adequate deletion of leukemic cells. Enzymatic treatment to disperse the testicular cells and feature of the intratesticular environment contributed to this immunophenotypic variation. Only germ cell selection in combination with leukemic cell deletion prevented leukemia transmission in association with intratesticular injection of the sorted cells. However, with such combined sorting, only 0.23% of the original testicular cells were recovered. With presently available techniques, flow cytometric purification of germ cells from a leukemic donor is not sufficiently effective or safe for clinical use.

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Phenotype and Natural Killer Cell Sensitivity of a Radiation‐Induced Acute T‐Cell Leukaemia (Roser Leukaemia) in PVG Rats

Cited by 11 publications

References 25 publications

Immunomagnetic separation of normal rat testicular cells from Roser’s T‐cell leukaemia cells is ineffective

Immunomagnetic separation of normal rat testicular cells from Roser’s T‐cell leukaemia cells is ineffective

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

Decontamination of leukemic cells and enrichment of germ cells from testicular samples from rats with Roser’s T-cell leukemia by flow cytometric sorting

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