PMID- 15541790
OWN - NLM
STAT- MEDLINE
DCOM- 20041230
LR  - 20141120
IS  - 0165-2427 (Print)
IS  - 0165-2427 (Linking)
VI  - 102
IP  - 4
DP  - 2004 Dec 28
TI  - The proliferation inhibitory proteins p27(Kip1) and retinoblastoma are involved 
      in the control of equine lymphocyte proliferation.
PG  - 363-77
AB  - Observations in early equine pregnancy clearly reveal maternal immune recognition 
      of and response to the presence of the conceptus. Nevertheless, both maternal 
      cellular and humoral responses appear ineffective in destroying the developing 
      placenta and fetus in early pregnancy. Our previous studies had shown that the 
      pre-conditioned medium generated from the culture of equine invasive trophoblast 
      inhibited mitogen-induced lymphocyte proliferation and the expression of cytokine 
      messenger RNA in vitro. Those findings also suggested that lymphocytes might have 
      been halted in the G0/G1 phase of the cell cycle. To characterize the cell cycle 
      and the intracellular mechanisms involved in the inhibition of lymphocyte 
      proliferation, equine peripheral blood lymphocytes were cultured in the presence 
      or absence of pokeweed mitogen (PWM) in fresh medium, or in medium 
      pre-conditioned through cell culture of invasive trophoblast cells or fetal 
      fibroblasts. Two-color flow cytometric analysis for bromodeoxyuridine (BrdU) 
      incorporation by stimulated lymphocytes, and concomitant DNA staining with 
      7-amino-actinomycin D (7-AAD), indicated that a greater proportion of lymphocytes 
      were found in the G0/G1 phase of the cell cycle when cultured in the invasive 
      trophoblast cell pre-conditioned medium compared to controls. Analysis using 
      carboxyfluorescein diacetate succinimidyl ester (CFSE) fluorescence intensity 
      demonstrated that lymphocytes cultured in the presence of invasive trophoblast 
      cell pre-conditioned medium had fewer cells going through division, but that 
      those fewer cells sustained similar numbers of cell divisions as in control 
      cultures. Hypophosphorylated retinoblastoma (Rb) protein expression was increased 
      and p27Kip1 expression was maintained at higher levels in lymphocytes cultured in 
      invasive trophoblast pre-conditioned medium compared to fresh medium. In 
      agreement with these data, flow cytometric measurement of the Ki-67 protein 
      expression in lymphocytes cultured in invasive trophoblast pre-conditioned medium 
      was lower in comparison to controls. These findings suggest that the equine 
      lymphocyte proliferation is at least partially regulated by the expression of 
      proliferation inhibitory proteins such as p27Kip1 and hypophosphorylated Rb. 
      These proteins seem to be important regulators of cell cycle transition between 
      G1 and S phase in equine lymphocytes.
FAU - Flaminio, M Julia B F
AU  - Flaminio MJ
AD  - Baker Institute for Animal Health, College of Veterinary Medicine, Cornell 
      University, Ithaca, NY 14853, USA. mbf6@cornell.edu
FAU - Yen, Andrew
AU  - Yen A
FAU - Antczak, Douglas F
AU  - Antczak DF
LA  - eng
GR  - HD-15799/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Vet Immunol Immunopathol
JT  - Veterinary immunology and immunopathology
JID - 8002006
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Cycle Proteins/biosynthesis/*immunology
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Culture Media, Conditioned
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Female
MH  - Gene Expression
MH  - HL-60 Cells
MH  - Horses/*immunology
MH  - Humans
MH  - In Vitro Techniques
MH  - Lymphocytes/*immunology/metabolism
MH  - Retinoblastoma Protein/biosynthesis/*immunology
MH  - Tumor Suppressor Proteins/biosynthesis/*immunology
EDAT- 2004/11/16 09:00
MHDA- 2004/12/31 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/03/04 00:00 [received]
PHST- 2004/06/30 00:00 [revised]
PHST- 2004/07/22 00:00 [accepted]
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2004/12/31 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - S0165-2427(04)00210-7 [pii]
AID - 10.1016/j.vetimm.2004.07.001 [doi]
PST - ppublish
SO  - Vet Immunol Immunopathol. 2004 Dec 28;102(4):363-77. doi: 
      10.1016/j.vetimm.2004.07.001.