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Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer.

Bauernhofer T, Kuss I, Friebe-Hoffmann U, Baum AS, Dworacki G, Vonderhaar BK, Whiteside TL - Br. J. Cancer (2003)

Bottom Line: In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004).Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006).Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.

ABSTRACT
Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

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Correlation between sFasL in plasma and expression of Fas on CD3+ T cells in the patients with BC and normal controls. The P-value shown is for combined analysis of patients and controls. When cord blood samples were included, the P-value was 0.0001.
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fig4: Correlation between sFasL in plasma and expression of Fas on CD3+ T cells in the patients with BC and normal controls. The P-value shown is for combined analysis of patients and controls. When cord blood samples were included, the P-value was 0.0001.

Mentions: In order to attempt to explain the mechanisms responsible for the higher onset of early apoptosis in CD95+ T cells in patients with breast cancer, we next determined plasma levels of sCD95L in the cohorts of patients and controls. The expectation was that sCD95L might be utilised in patients through its binding to CD95 expressed on T cells. Indeed, a statistically significant lower level of sCD95L was found in patients compared to normal controls and cord blood, as shown in Table 2. Those breast cancer patients with the highest percentage of CD95+ CD3+ T cells had the lowest sCD95L levels in the plasma (Figure 4Figure 4


Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer.

Bauernhofer T, Kuss I, Friebe-Hoffmann U, Baum AS, Dworacki G, Vonderhaar BK, Whiteside TL - Br. J. Cancer (2003)

Correlation between sFasL in plasma and expression of Fas on CD3+ T cells in the patients with BC and normal controls. The P-value shown is for combined analysis of patients and controls. When cord blood samples were included, the P-value was 0.0001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747567&req=5

fig4: Correlation between sFasL in plasma and expression of Fas on CD3+ T cells in the patients with BC and normal controls. The P-value shown is for combined analysis of patients and controls. When cord blood samples were included, the P-value was 0.0001.
Mentions: In order to attempt to explain the mechanisms responsible for the higher onset of early apoptosis in CD95+ T cells in patients with breast cancer, we next determined plasma levels of sCD95L in the cohorts of patients and controls. The expectation was that sCD95L might be utilised in patients through its binding to CD95 expressed on T cells. Indeed, a statistically significant lower level of sCD95L was found in patients compared to normal controls and cord blood, as shown in Table 2. Those breast cancer patients with the highest percentage of CD95+ CD3+ T cells had the lowest sCD95L levels in the plasma (Figure 4Figure 4

Bottom Line: In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004).Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006).Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.

ABSTRACT
Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

Show MeSH
Related in: MedlinePlus