Tumour rejection after adoptive transfer of line-10-immune spleen cells is mediated by two T cell subpopulations

Steerenberg, P. A.; Geerse, E.; Jong, Wim H. de; Bürger, Reinhard; Scheper, Rik J.; Otter, W. Den

doi:10.1007/bf01741343

Cited by 6 publications

(2 citation statements)

References 24 publications

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“…Five-micrometer-thick cryostat sections were stained with the following monoclonal antibodies: H159, which recognizes a framework determinant of the guinea pig T cell receptor (TCR), and which was also characterized by biochemical and functional assays as being a mature T-lymphocyte marker (12); H155,characterized as reacting against guinea pig CD4+, either by immunohistology in different tissues, biochemical studies, or depletion experiments and/or functional studies (13); and CT6, described as staining a subpopulation of T-lymphocyteswith a distribution similar to CD8 + T cells in other species (14). Subsequent work demonstrated that H155and CT6 stained different populations of T cells and that CT6 blocked the cytotoxic T lymphocyte (CTL) activity of Tcelllines (15). For the mouse antibody (CT6), an alkaline phosphatase-antialkaline phosphatase (APAAP) staining procedure was performed as previously described (16), using rabbit immunoglobulin (Ig) to mouse Ig (Z259; Dakopatts a/s, Copenhagen, Denmark) and mouse APAAP (D651, Dakopatts a/s), followed by incubation with the substrate Fast Red TR (Sigma) and naphthol AS MX phosphate (Sigma), and light hematoxylin counterstaining.…”

Section: Immunohistochemistry Techniquesmentioning

confidence: 98%

Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate.

Mapp¹,

Silva²,

Lucchini³

et al. 1996

Am J Respir Crit Care Med

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Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational lung disease. We used a model to investigate the course of bronchopulmonary inflammation following immunization with TDI. Guinea pigs were immunized by weekly intradermal injections and challenged with TDI 7 d after the third injection. The animals were killed at different times after challenge and prepared for histologic examination of central and peripheral airways, for immunohistochemical studies of T lymphocyte and eosinophil distribution, and for hematologic and serologic investigations. Specific IgG1 against TDI were present only in immunized animals. In immunized TDI-challenged animals there was a significant increase in the number of metachromatic cells (at 24 h) and a late increase of eosinophils (at 48 h) in the peripheral blood. Mast cells and eosinophils were also increased in the submucosa of central airways of immunized TDI-challenged animals. A similar pattern was observed in the animals' peripheral airways. Additionally, a significant increase of T-lymphocytes and eosinophils was found in the lamina propria at 6 h after exposure in immunized TDI-challenged animals as compared with control animals. In these immunized animals, TDI challenge caused a significant increase of eosinophils, T-lymphocytes, and CD4+ T cells. These findings indicate that intradermal injections of TDI induced a specific antibody response as well as an inflammatory process in both central and peripheral airways. T cells, particularly CD4+ T cells and eosinophils, are the key cells in the immunopathologic alterations induced by TDI in the guinea pig lung.

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Section: Immunohistochemistry Techniquesmentioning

confidence: 98%

Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate.

Mapp¹,

Silva²,

Lucchini³

et al. 1996

Am J Respir Crit Care Med

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“…Adoptive T cell transfer may become an effective treatment for HCCs [79,80]. In an early study [81] indium-labelled TIL were injected in the hepatic artery of patients with hepatic malignancies to determine their in vivo distribution.…”

Section: Passive Specific Immunotherapy Of Hccsmentioning

confidence: 99%

Immunobiology and Gene-Based Immunotherapy of Hepatocellular Carcinoma

Geißler

Mohr²,

Ali³

et al. 2003

Z Gastroenterol

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Until now, a variety of specific and non-specific immunostimulatory strategies against HCC has been applied in preclinical experimental models with some promising results. The molecular characterization of HCC associated tumour antigens such as alpha-fetoprotein (AFP) and the increased understanding of the immunological pathways involved in liver and tumor immunology have paved the way for the design of promising gene-based cancer vaccines. The first phase I and II immunotherapeutic clinical trials based on dendritic cell immunotherapy and peptide vaccines are ongoing in HCC-patients. Clinical trials have, in general, demonstrated the safety of such strategies. Recently, exciting new immunological techniques and tools have been developed which allow to characterize antigen specific T cells at a single-cell level. In future, HCC specific tumor rejection antigens which can be used therapeutically have to be identified using microarray-based analysis. The different therapeutic modalities need to be compared directly resulting in optimised therapeutic approaches and the identification of sub-groups of HCC-patients responding favourably to treatment.

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Locoregional therapy with polyethylene-glycol-modified interleukin-2 of an intradermally growing hepatocellular carcinoma in the guinea pig induces T-cell-mediated antitumor activity

Balemans

Mattijssen

Steerenberg

et al. 1993

Cancer Immunol Immunother

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Therapy with repeated intratumoral and perilymphatic administration of relatively low doses of polyethylene-glycol(PEG)-modified interleukin-2 (IL-2) in the syngeneic guinea pig line 10 (L10) hepatocarcinoma results in significant local tumor growth inhibition and a delay in development of regional lymph node metastases of more than 3 weeks when compared to controls. Occasionally animals are cured of tumor. The mechanism of this antitumor activity was studied. The antitumor activity of locoregionally administered PEG-IL-2 was abrogated by pretreatment with polyclonal anti-thymocyte serum, indicating that the observed tumor growth inhibition was a T-cell-mediated phenomenon. Besides the locoregional tumor growth inhibition, a systemic effect was recorded as the growth of a second tumor cell inoculum at the contralateral side was inhibited as well. Furthermore, those animals cured after PEG-IL-2 therapy developed specific immunity against the L10 tumor and this immunity could be transferred to naive animals by spleen cells. Immunohistological observations of the tumor site revealed a slight increase of helper and cytotoxic T cell subpopulations after PEG-IL-2 therapy. More pronounced, however, was the rise in number of eosinophilic granulocytes present in the stroma surrounding the tumor cells. Involvement of cytotoxic cells in the antitumor effects of PEG-IL-2 could not be demonstrated: regional lymph node cells and spleen cells obtained immediately after therapy (day 15) or on day 21 showed no cytotoxic activity in vitro against L10, K562, Daudi and line 1 (L1) target cells. In conclusion, locoregional therapy with PEG-IL-2 induced a a systemic T-cell-mediated antitumor response. As no cytotoxic T cell activity was measured, however, the underlying mechanism is most likely a T-helper response. Eosinophils at the tumor site may be tumoricidal but further experiments must reveal the role of these cells in the PEG-IL-2-induced tumor regression.

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Tumour rejection after adoptive transfer of line-10-immune spleen cells is mediated by two T cell subpopulations

Abstract: Offprint requests to: P. A. Steerenberg approach of in vitro expanded TIL cells should take into consideration the requirement of two T cell subsets.

Cited by 6 publications

References 24 publications

Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate.

Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate.

Immunobiology and Gene-Based Immunotherapy of Hepatocellular Carcinoma

Locoregional therapy with polyethylene-glycol-modified interleukin-2 of an intradermally growing hepatocellular carcinoma in the guinea pig induces T-cell-mediated antitumor activity

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