Different T-cell activation by streptozotocin and freund's adjuvant in popliteal lymph node (PLN)

Krzystyniak, Krzysztof; Kozłowska, Ewa; Desjardins, Richard; Drela, Nadzieja; Kowalczyk, Renata; Karwowska, Katarzyna; Izdebska-Szymona, K

doi:10.1016/0192-0561(94)00100-3

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…Consistent with previous studies [24, 25], enlargement of the lymph nodes was recognized at day 7 after either tumor cell inoculation or CFA administration (Fig. 2).…”

Section: Resultssupporting

confidence: 92%

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

et al. 2012

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Objectives Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI). Materials and methods Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or Complete Freund Adjuvant (CFA) in male Balb/C mice. At different time points after inoculation, bioluminescence imaging, T2-weighted, diffusion-weighted and SPIO enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Results Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging (DWI). At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 ± 0.03 × 10−3 mm2/s than that of RLNs (0.34 ± 0.02 10−3 mm2/s, p < 0.05). On SPIO enhanced MRI, both TLNs and RLNs showed distinct T2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Conclusions Both diffusion-weighted and SPIO enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages.

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“…Consistent with previous studies [24, 25], enlargement of the lymph nodes was recognized at day 7 after either tumor cell inoculation or CFA administration (Fig. 2).…”

Section: Resultssupporting

confidence: 92%

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

et al. 2012

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“…In good correlation with the basic PLN cell count indices, [Pt(NH3)4]Cl2 completely failed to generate PLN T-cell activation as reflected by proliferation o f CD4+ lym phocytes when compared with saline-treated controls. The discrimination between sensitizing and nonsensitizing compounds by this nonradioactive and fast phenotype anal ysis of proliferating cells in vivo appears to be more sensi tive than monitoring activation markers at the cell surface such as CD25 or CD69 [25].…”

Section: Discussionmentioning

confidence: 99%

Immunostimulatory Effects of Platinum Compounds: Correlation between Sensitizing Properties in vivo and Modulation of Receptor-Mediated Endocytosis in vitro

Schuppe

Kulig

Kühn³

et al. 1997

Int Arch Allergy Immunol

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The sensitizing properties of different complex salts of platinum were defined in vivo by means of the popliteal lymph node (PLN) assay in mice. Hexa- and tetrachloroplatinates were confirmed to be highly immunogenic, inducing vigorous primary immune responses in the draining PLN following single subcutaneous injections. Flow-cytometric analysis revealed a dramatic increase in the total number of cells expressing proliferating cell nuclear antigen. The majority of these cells were of the T helper phenotype (CD4+) reflecting the T-cell dependence of the PLN response induced by Pt salts such as Na₂[PtCl₆] or Na₂[PtCl₄]. In contrast, [Pt(NH₃)₄]Cl₂ failed to elicit a significant increase in PLN cell proliferation when compared with saline-treated controls. The differential immunogenicity of the Pt compounds found in vivo directly correlated with their capacity to modulate mechanisms of receptor-mediated endocytosis in murine Langerhans cells in vitro. The reactivity of Na₂[PtCl₆] or Na₂[PtCl₄] resembled that of potent contact sensitizers in this endocytosis assay whereas [Pt(NH₃)₄]Cl₂ proved to be inert. These results suggest that [Pt(NH₃)₄]Cl₂ might be less harmful to humans than hexa- or tetrachloroplatinates. As demonstrated with Pt compounds, monitoring of direct effects of low-molecular-weight chemicals on antigen-presenting dendritic cells in vitro is able to predict their sensitizing potential in vivo.

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“…To date, positive responses in the direct PLNA are more likely to reflect varied mechanisms, even though T lymphocytes often have been suggested to play a pivotal role (Klinkhammer et al, 1988;Ewens et al, 1999;Tuschl et al, 2002). Indeed, PLN responses can be induced also by macrophage activation (Weirich et al, 1996) or non-specific inflammatory responses (Krzystyniak et al, 1995;Choquet-Kastylevsky and Descotes, 2004), although rarely. As long as no elucidation of the underlying mechanism(s) is available, the search for endpoints other than WI and CI to assess better the relevance of a positive response to a given compound in the PLNA is difficult, if at all possible.…”

Section: Limits and Perspectivesmentioning

confidence: 98%

Popliteal lymph node assay: facts and perspectives

Ravel¹,

Descotes²

2005

J. Appl. Toxicol.

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The popliteal lymph node assay (PLNA) derives from the hypothesis that some supposedly immune-mediated adverse effects induced by certain pharmaceuticals involve a mechanism resembling a graft-versus-host reaction. The injection of many but not all of these compounds into the footpad of mice or rats produces an increase in the weight and/or cellularity of the popliteal lymph node in the treated limb (direct PLNA). Some of the compounds known to cause these adverse effects in humans, however, failed to induce a positive PLNA response, leading to refinements of the technique to include pretreatment with enzyme inducers, depletion of CD4(+) T cells or additional endpoints such as histological examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative approaches have been used to improve further the predictability of the assay. In the secondary PLNA, the test compound is injected twice in order to illicit a greater secondary response, thus suggesting a memory-specific T cell response. In the adoptive PLNA, popliteal lymph node cells from treated mice are injected into the footpad of naive mice; a marked response to a subsequent footpad challenge demonstrates the involvement of T cells. Finally, the reporter antigens TNP-Ficoll and TNP-ovalbumin are used to differentiate compounds that induce responses involving neo-antigen help or co-stimulatory signals (modified PLNA). The PLNA is increasingly considered as a tool for detection of the potential to induce both sensitization and autoimmune reactions. A major current limitation is validation. A small inter-laboratory validation study of the direct PLNA found consistent results. No such study has been performed using an alternative protocol. Other issues include selection of the optimal protocol for an improved prediction of sensitization vs autoimmunity, and the elimination of false-positive responses due to primary irritation. Finally, a better understanding of underlying mechanisms is essential to determine the most relevant endpoints. The confusion resulting from use of the PLNA to predict autoimmune-like reactions as well as sensitization should be clarified. Interestingly, most drugs that were positive in the direct PLNA are also known to cause drug hypersensitivity syndrome in treated patients. This observation is expected to open new avenues of research.

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Different T-cell activation by streptozotocin and freund's adjuvant in popliteal lymph node (PLN)

Cited by 8 publications

References 17 publications

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

Immunostimulatory Effects of Platinum Compounds: Correlation between Sensitizing Properties in vivo and Modulation of Receptor-Mediated Endocytosis in vitro

Popliteal lymph node assay: facts and perspectives

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