Activation of suppressor T cells by low-molecular-weight factors secreted by spleen cells from tumor-bearing mice

Pope, Barbara L.

doi:10.1016/0008-8749(85)90141-8

Cited by 13 publications

(4 citation statements)

References 36 publications

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“…2). This observation clearly distinguishes the activity of SUF from that of suppressive agents like cyclosporine A [19,20] and soluble suppressive mediators such as those described by Malkovsky et al [21] and by Pope [22] that were shown to impair T cell activity by inhibiting the synthesis of IL 2.…”

Section: Discussionmentioning

confidence: 90%

Soluble factors secreted by naturally occurring suppressor cells that interfere with in vivo graft‐vs.‐host disease and with T cell responsiveness in vitro

Knaän‐Shanzer

Bekkum

1987

Eur J Immunol

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A potent immunosuppressive factor (SUF) is found in the supernatant of short-term cultures of unstimulated thymocytes or spleen cells of neonatal mice and rats and in culture medium of hybridoma cell lines established by fusing neonatal mouse spleen cells with T lymphoma cells (the BW 5147 line). In vitro incubation of spleen cells with SUF suppresses the acute in vivo graft-vs.-host disease, normally induced by allogeneic spleen cells in lethally irradiated mice. Incubation of bone marrow cells with SUF does not affect the hemopoietic stem cells. The addition of SUF to mixed lymphocyte reaction cultures strongly suppresses lymphocyte proliferation. The non-species-restricted inhibition of cell proliferation induced by SUF is shown not to be due to toxicity or nonspecific interference with DNA synthesis. Molecular size fractionation of crude SUF revealed two active moieties: a large moiety of molecular mass greater than 100 kDa and a small moiety of less than 3 kDa. The high kDa moiety mediates T cell unresponsiveness both in vivo and in vitro. In vitro studies revealed that this moiety primarily affects an early event in the proliferative response to alloantigen and mitogen, that prevents interleukin 2 (IL 2) receptor expression and, consequently, blastogenesis and DNA duplication. It does not affect, however, the synthesis of IL 2. The suppressive activity of the low kDa moiety can be demonstrated only in in vitro systems. Pre-treatment of donor lymphocytes with this fraction cannot prevent graft-vs.-host disease mortality. The inhibition of cell proliferation induced by this fraction in vitro is most likely due to interference with the utilization of IL 2, as suggested by its suppressive effect on the proliferation of CTLL-2 cells (an IL 2-dependent cell line).

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Section: Discussionmentioning

confidence: 90%

Soluble factors secreted by naturally occurring suppressor cells that interfere with in vivo graft‐vs.‐host disease and with T cell responsiveness in vitro

Knaän‐Shanzer

Bekkum

1987

Eur J Immunol

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“…Certain tumor cells are capable of producing soluble suppressor factors, for example prostaglandins of the E series (PGE) [6][7][8] which can directly suppress all cells of the immune system [9]. Secondly, tumor development may result in the induction of tumor-specific as well as non-specific suppressor mechanisms within the host [10,11]. Amongst the latter category, induction of PGE production by host macrophages in the lymphoid organs as well as at the tumor site appears to be a common phenomenon [12,13], which in turn can inactivate all tumoricidal effector cell lineages such as T-cells, NK cells and macrophages [14], and may also induce generation of T suppressor cells [151.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2

et al. 1992

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In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E2 (PGE2)-mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 micrograms/ml of water) or Indo (CIT; 10 micrograms/ml) 5 days after s.c. transplantation of 5 x 10(5) metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 micrograms/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1+, Thy-1-, Lyt-2- phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20-23, 31-34) of IL-2 (15,000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1+, Thy-1-, Lyt-2-); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1+, Thy-1+ and Lyt-2+ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu+IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE2 synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Suppressor ceils and their products have been identified in tumour-bearing hosts and are also implicated as the major cause of the immune suppression observed in these hosts (4,5). These suppressor cells have been characterized as macrophages (6), T cells (7) or B cells (8).…”

Section: Introductionmentioning

confidence: 99%

“…It has been known for some time that many progressively growing tumours are associated with or may lead to the impairment of both humoral and cellular Immune functions (1)(2)(3). Suppressor ceils and their products have been identified in tumour-bearing hosts and are also implicated as the major cause of the immune suppression observed in these hosts (4,5). These suppressor cells have been characterized as macrophages (6), T cells (7) or B cells (8).…”

Section: Introductionmentioning

confidence: 99%

Depression of cell‐mediated immunity in plasmacytoma‐bearing mice

Ruszala-Mallon¹,

Silva²,

Lumanglas³

et al. 1991

Immunology & Cell Biology

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Summary Previous reports have documented that mice bearing plasmacytomas (PC) are suppressed in their ability to mount a primary antibody response, whereas cellular immunity appears to be normal. Studies presented here provide evidence that T cell responsiveness is also depressed in BALB/c mice bearing the Lieberman plasmacytoma (Lpc-1). For instance, splenocytes from mice bearing large tumours were impaired in their in vitro ability to respond to the T cell mitogen, mount an appropriate alloreactive cytolytic T lymphocyte response, and produce interleukin-2 {IL-2). A population of suppressor cells was detected in the spleens 7 days after tumour implantation as evidenced by their ability to prevent normal splenocytes not only from responding to antigens in mixed lymphocyte culture, but also from producing IL-2. A similar inhibitory effect was observed with culture supematants of these cells, indicating the existence of a soluble suppressive factor. Therefore, the present study demonstrates that cellular immune responses ar« impaired in mice bearing Lpc-1 tumours and that this effect may be due to the generation of suppressor cells and/or a suppressive factor.

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Activation of suppressor T cells by low-molecular-weight factors secreted by spleen cells from tumor-bearing mice

Cited by 13 publications

References 36 publications

Soluble factors secreted by naturally occurring suppressor cells that interfere with in vivo graft‐vs.‐host disease and with T cell responsiveness in vitro

Soluble factors secreted by naturally occurring suppressor cells that interfere with in vivo graft‐vs.‐host disease and with T cell responsiveness in vitro

Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2

Depression of cell‐mediated immunity in plasmacytoma‐bearing mice

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