title: Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer.
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.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bauernhofer
authors.forename: I
authors.initials: I
authors.lastname: Kuss
authors.forename: U
authors.initials: U
authors.lastname: Friebe-Hoffmann
authors.forename: A S
authors.initials: AS
authors.lastname: Baum
authors.forename: G
authors.initials: G
authors.lastname: Dworacki
authors.forename: B K
authors.initials: BK
authors.lastname: Vonderhaar
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005312:Fetal Blood; D006801:Humans; D019169:Jurkat Cells; D008875:Middle Aged; D009367:Neoplasm Staging; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011981:Receptors, Prolactin / Q000502:physiology*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015375:Receptors, Interleukin-2; D011981:Receptors, Prolactin; D019014:fas Receptor