The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice

Singer, Gary G.; Abbas, Abul K.

doi:10.1016/1074-7613(94)90067-1

Cited by 675 publications

(423 citation statements)

References 43 publications

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“…As our in situ results indicate, and as has previously been shown for peripheral lymphoid tissue [20], Fas is involved in peripheral deletion of autoreactive T cells. Accelerated spontaneous apoptosis of lymph node lpr T cells in vitro has previously been reported [23].…”

Section: Discussionsupporting

confidence: 91%

Lymphoid Cell Accumulation in Salivary Glands of Autoimmune MRL Mice Can be Due to Impaired Apoptosis

Skarstein

Nerland

et al. 1997

Scand J Immunol

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MRL-lpr mice and the congenic strain MRL þ/þ exhibit pathological abnormalities in the salivary glands similar to Sjögren's syndrome in humans. The lpr genotype has been identified as a mutation in the gene encoding Fas which is a cell surface protein that mediates apoptosis. The mutation is leaky, allowing for low levels of the APO-1/Fas (CD95) receptor and partial activity of Fas/Fas ligand-mediated programmed cell death in this strain. To examine the expression of Fas in situ, the authors analysed thymus, lymph node and salivary gland tissue from BALB/c, MRL þ/þ and MRL-lpr mice by an immunohistochemical technique (ABC-immunoperoxidase) using an anti-Fas (Jo2) antibody. For detection of apoptotic cells the authors used the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling (TUNEL) method. Thymus from MRL þ/þ and normal BALB/c mice showed a higher frequency of Fas expression than was seen in the lpr mice, but the þ/þ mice had similar expression of Fas in lymph nodes as lpr mice. The Fas protein was detected among infiltrating mononuclear cells in the salivary glands of both lpr and þ/þ mice. Apoptotic cells were found in the thymus with similar frequency in all three strains, while in the lymph nodes only BALB/c mice showed apoptosis. There was no, or very low, frequency of apoptosis among infiltrating mononuclear cells in salivary glands of both MRL strains. In conclusion, despite mutation of the Fas gene in the MRL-lpr strain, there was nevertheless an expression of the apoptosis-related Fas protein in lymphoid tissue and salivary glands of these mice. Based on analysis of apoptotic activity, the impaired Fas in autoimmune MRL mice seems to affect primarily the peripheral organs.

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Section: Discussionsupporting

confidence: 91%

Lymphoid Cell Accumulation in Salivary Glands of Autoimmune MRL Mice Can be Due to Impaired Apoptosis

Skarstein

Nerland

et al. 1997

Scand J Immunol

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“…CD95, one of the most extensively studied death receptors was shown early on not to be involved in thymocyte deletion [33]. This was surprising because thymocytes express CD95, and thymic epithelial cells express CD95L.…”

Section: Apoptosis In the Immune System Central Tolerance -Education mentioning

confidence: 99%

How apoptosis got the immune system in shape

Feig

Marynen

2007

Eur. J. Immunol.

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“…Apoptosis is an important immunoregulatory mechanism, which is tightly controlled by a network of a rapidly growing list of apoptosis inhibiting (bcl-2, bcl-x L , bag-1) [1][2][3] and inducing (fas/Apo-1, fas-L, bax, bak, bad, c-myc) proteins [4][5][6][7][8][9][10][11][12][13]. Induction of apoptosis can be initiated or prevented by signals though cell membrane proteins (CD2, CD3, CD4 or others) or by soluble factors like interleukin (IL)-2, IL-7, IL-4, G-or GM-CSF [14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

et al. 1997

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Lorenz H-M, Hieronymus T, Grünke M, Manger B, Kalden JR. Differential Role for IL-2 and IL-15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes. Scand J Immunol 1997;45:660-669 Interleukin (IL)-15 is a newly described cytokine with properties similar to IL-2. Even though it does not share sequence homology with IL-2, both cytokines bind to the same receptor with the noted exception of a cytokine specific a-chain. In this study the authors compared IL-2 and IL-15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death. The authors found that both IL-2 and IL-15 can inhibit induction of apoptosis in this experimental model with similar time and dose kinetics. On mRNA or protein levels induction of pro-and anti-apoptotic gene products like fasL, bcl-2, or bax with minor effects on fas/Apo-1 or bcl-x L was observed under culture conditions with both IL-2 and IL-15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cellular proliferation and prevention from apoptosis) to IL-2 if signals through the a-chain were blocked, with no effect on b-chain specific monoclonal antibodies (MoAb). By contrast, IL-15 was less effective in induction of cellular proliferation and prevention of apoptosis if IL-2R b-chain specific MoAb were added to cell cultures. Testing intracellular signalling induced by IL-2 or IL-15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL-2 or IL-15 stimulation. By contrast, they found consistent differences if PHA stimulated peripheral blood mononuclear cells (PBMC) were expanded in medium containing IL-15 (instead of IL-2). These IL-15 expanded PHA blasts showed a significantly increased percentage of apoptosis after growth factor withdrawal. Furthermore, IL-2 was more efficient than IL-15 in rescuing IL-15 expanded PHA blasts from apoptosis. In IL-15 expanded PHA blasts expression of IL-2R a-chain was lower than that in IL-2 expanded PHA blasts. A model presenting a differential role for IL-2 and IL-15 in inhibition of apoptosis in vivo is discussed.

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The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice

Cited by 675 publications

References 43 publications

Lymphoid Cell Accumulation in Salivary Glands of Autoimmune MRL Mice Can be Due to Impaired Apoptosis

Lymphoid Cell Accumulation in Salivary Glands of Autoimmune MRL Mice Can be Due to Impaired Apoptosis

How apoptosis got the immune system in shape

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

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