Lymphokines and the immune response: the central role of interleukin-2

Swain, Susan L.

doi:10.1016/0952-7915(91)90028-y

Cited by 97 publications

(39 citation statements)

References 47 publications

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“…Survival of these cells depends on the presence of cytokines; IL-2, IL-4 and IL-15 and seem to effective [3]. In addition, IL-2 is well documented to promote proliferation of activated T cells [18]. Furthermore, IL-2 has been shown to protect activated T cells against cell deathinducing stimuli such as radiation and dexamethasone, partly by up-regulating the cellular proteins bcl-2 and bcl-x [5,17].…”

Section: Discussionmentioning

confidence: 99%

Activation of caspase-3-like enzymes in non-apoptotic T cells

1998

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The activation of the caspase family of cysteine proteases is a key step in the implementation of apoptotic cell death leading to further downstream effects such as DNA fragmentation. In cultured tumor cells, caspase activity appears only when cells are undergoing apoptosis. Here we show that human and murine T lymphocytes acquire high intracellular activities of cell death-specific caspases upon activation by mitogens and IL-2 without evidence that apoptosis is proceeding. The highest activity is seen when cells are mitogen activated for 3 days. On a per cell basis, caspase activity in activated T cells is much higher than in tumor cells induced to undergo apoptosis. In the presence of exogenously added IL-2 cells stay alive and maintain a high level of caspase activity while IL-2 withdrawal results in cell death and decline of caspase activity. Caspase activity can also be measured in extracts from spleen and lymph nodes from mice injected with superantigen. While in tumor cell lines caspase activity correlates with cleavage of poly(ADP)-ribose polymerase (PARP) and DNA fragmentation, in activated T cells cleavage products of cellular PARP can be detected whereas DNA fragmenting activity appears only upon IL-2 withdrawal which coincides with cell death. These data show that caspase activation in intact cells does not necessarily lead to cell death and argue for a checkpoint in the apoptotic pathway downstream of caspases. Furthermore, they provide a molecular correlate for the high susceptibility of activated T cells for apoptosis.

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Section: Discussionmentioning

confidence: 99%

Activation of caspase-3-like enzymes in non-apoptotic T cells

1998

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“…IFNs, IL-2, and IL-12, cytokines that induce hormone sensitivity and stimulate cellular immunity, have also been used to treat advanced breast cancer (Swain 1991;Fehniger and others 2002;Hsing and others 2012). Although treatment with IL-2 or IL-6 alone, IL-2 combined with IFN-a, G-CSF or trastuzumab, and IL-12 and trastuzumab is well tolerated (Nicolini and others 2006), they had no clear antitumor effect or have improvement beyond each individual treatment.…”

Section: Cytokines and Breast Cancer Treatmentmentioning

confidence: 99%

The Role of Cytokines in Breast Cancer Development and Progression

Esquivel-Velázquez

Ostoa‐Saloma

Palacios-Arreola

et al. 2015

Journal of Interferon & Cytokine Research

427

363

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Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancerrelated disorders.

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“…IFN-c decreases the production of IL-2 IL-2 is important for the generation of CTL activity in MLC (13,14). Thus one mechanism by which IFN-c could regulate CTL activity in culture would be to control IL-2 production.…”

Section: The Effect Of Ifn-c or Ifn-c R1 Deficiency On Ctl Generationmentioning

confidence: 99%

IFN-γ Decreases CTL Generation by Limiting IL-2 Production: A Feedback Loop Controlling Effector Cell Production

Hidalgo

Urmson

Halloran

2005

American Journal of Transplantation

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IFN-c is produced by cytotoxic T lymphocytes (CTL)but can also decrease CTL generation. We used IFN-c -R1-deficient (GRKO) and IFN-c -deficient (GKO) mice to study the effects of IFN-c in MLC on the generation of CTL activity and CTL number, IL-2 production and cell proliferation. CTL activity was increased in MLC when GRKO responders or GKO stimulators and responders were used, compared to wild-type (WT) MLC. The number of cells displaying the CTL phenotype (CD3 + , CD8 + , CD25 + ) was also increased, accompanied by increased IL-2 production and proliferation. Combinations of WT or GRKO CD4+ T cells with WT or GRKO CD8+ T cells as responders showed that IFN-c mostly affects CD4+ T cells to limit CTL generation. Intracellular staining indicated that IL-2 production was largely by CD4+ T cells. Moreover, addition of IL-2 to WT responders mimicked GKO CTL generation and activity, whereas neutralizing IL-2 decreased CTL activity in GRKO and WT responders. Thus IFN-c reduces CTL generation in alloimmune responses largely by limiting proliferation of IL-2 producing CD4+ T cells. This creates a feedback loop in which effectors produce IFN-c that limits IL-2 production which in turn limits CTL generation.

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Lymphokines and the immune response: the central role of interleukin-2

Cited by 97 publications

References 47 publications

Activation of caspase-3-like enzymes in non-apoptotic T cells

Activation of caspase-3-like enzymes in non-apoptotic T cells

The Role of Cytokines in Breast Cancer Development and Progression

IFN-γ Decreases CTL Generation by Limiting IL-2 Production: A Feedback Loop Controlling Effector Cell Production

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