Suppression by sorted CD8+CD11b− cells from T-cell growth factor-activated peripheral blood lymphocytes on cytolytic activity against tumour in patients with gastric carcinoma

Ebihara, Tadashi; Sakai, Norie; Koyama, Shohei

doi:10.1016/0277-5379(91)90439-k

Cited by 10 publications

(9 citation statements)

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“…We decided to measure the degree of expression of the CD11b membrane antigen on CD8 + proliferating cells. The proliferating population was essentially CD11b − , having these CD8 + CD11b − lymphocytes been associated with immunosuppressive properties [ 32 ], indicating again that MSC would mainly be exerting their effect by affecting a regulatory subpopulation, as previously mentioned for Treg cells. Finally, we have also analysed the effect of CM obtained from the different clones on PBMC proliferation inhibition, being lower than the one observed under the presence of clones and only reaching a significant value for clone 1.22.…”

Section: Discussionmentioning

confidence: 99%

Differences of Clonogenic Mesenchymal Stem Cells on Immunomodulation of Lymphocyte Subsets

Martínez-Peinado

Pascual-García

Roche

et al. 2018

Journal of Immunology Research

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Mesenchymal stem cells (MSC) are a widely used population in cell therapy for their ability to differentiate into distinct tissues and more lately, for their immunomodulatory properties. However, the use of heterogeneous populations could be responsible for the nondesired outcomes reflected in the literature. Here, we analyse the different capacities of five one-cell-derived MSC clones to exert their immunomodulation ex vivo. We assessed proliferation assays in cocultures of MSC clones and purified cluster of differentiation (CD)3+, CD4+, or CD8+ lymphocytes; analysed the regulatory T (Treg) cells fold change rate; determined the effects on viability of peripheral blood mononuclear cells (PBMC); and also measured the coculture cytokine profiles (Th1/Th2). Conditioned media (CM) of different clones were also used to perform both proliferation assays and to analyse Treg fold change. The five clones analysed in this work were able to generate heterogeneous environments. Different clones inhibited proliferation of CD3+ and CD4+ lymphocytes, with different intensities. Surprisingly, all clones promoted proliferation of CD8+ lymphocytes. Different MSC clones and their CM were able to increase the number of Treg with different intensities. Finally, different clones also promoted different effects on the viability of PBMC treated with ultraviolet light. Considering all these data together, it seems that different clones, even from the same donor, can promote a wide spectrum of responses from anti-inflammatory to proinflammatory character. This fact may be important to standardise the design of personalized cell therapy protocols, thus diminishing the aforementioned undesired outcomes existing nowadays in this type of therapies.

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Section: Discussionmentioning

confidence: 99%

Differences of Clonogenic Mesenchymal Stem Cells on Immunomodulation of Lymphocyte Subsets

Martínez-Peinado

Pascual-García

Roche

et al. 2018

Journal of Immunology Research

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“…The concepts described in the reports are certainly based on experiments in animal systems and are not directly ready for clinical application. However, the basic observations about the suppressor-cell network in animal models have been found in humansystems (14)(15)(16)(17)(18), and a clinically useful application of the basic observations appears inevitable.…”

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confidence: 99%

“…The cells dominantly expressing CD8antigen were shown to inhibit the patient' s ownlymphoproliferativeresponses to alloantigen or phytohemagglutinin. Furthermore, it has been shown that TCGFactivated peripheral blood lymphocytes (PBL) from patients with advanced gastric carcinoma inhibited the effector process of tumor cell lysis by LAKcells which had been activated in vitro by rIL 2 (15,17). This suppression of cytotoxicity is exerted by blocking directly the activity of LAKcells.…”

mentioning

confidence: 99%

“…This suppression of cytotoxicity is exerted by blocking directly the activity of LAKcells. The effector cells responsible for suppression of LAKactivity showed surface phenotype of CD8+ CD1lb~in FACSsorting techniques (17). It has also been shown that freshly obtained PBL, especially nylon-wool adherent cells from patients with advanced gastric carcinoma directly inhibit the activity of CTL and LAK cells against tumor (18).…”

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confidence: 99%

“…These findings mean that therapeutic effect by the infusion ofCTL or LAKcells for adoptive immunotherapy will be directly inhibited by circulating CD8+ T and CD8" CD1 lb+ suppressor cells in patients with carcinoma. The generation of the suppressor cells seems to be a result of large tumor burden (14,15,17). In thepresence ofsuppressorcells, immunotherapy based on the CTLor LAKcells will be ineffective; therefore, immunotherapyneeds to be conducted after such suppressor Recently, Loeffler et al (20) reported that the decreased cytotoxic function of splenic CD8+ LAKcells generated by murine CD3and human recombinant IL 2 from late tumorbearing mice was not due to the presence of CD8+suppressor cells, but due to the impaired expression of granzyme B mRNA of the cells.…”

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confidence: 99%

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