Expanded cohorts of maternal CD8+ T-cells specific for paternal MHC class I accumulate during pregnancy.
A recombinant H-2Kb transgene, GK, containing the human HLA-G gene promoter is expressed throughout the trophoblast when inherited paternally. Male GK transgenic mice were mated with female T-cell receptor (TCR) transgenic mice to assess the effect of fetal H-2Kb expression on maternal H-2Kb-specific CD8+ T-cells during pregnancy. The number of maternal H-2Kb-specific CD8+ T-cells in spleen increased significantly (approximately 3-fold) 10 days post coitus when the GK transgene was inherited from the father. A smaller (approximately 2-fold) increase was observed in the spleen of pregnant females mated with C57BL/10 (H-2b) males. No increase was observed in mothers mated to syngeneic male mice. In both cases where expanded cohorts of maternal CD8+ T-cells were observed the amount of surface CD8 and to a lesser extent, TCR molecules was reduced. No change in the amount of surface CD44 or CD45RB was detected when levels were compared with naive T-cells from control virgin female mice. Expanded cohorts of CD8+ T-cells were also detected in para-aortic and inguinal lymph nodes draining the uterus but no changes were observed in mesenteric lymph nodes. This study concludes that maternal CD8+ T-cells are exposed to paternally inherited fetal MHC class I antigens during pregnancy. Moreover, the phenotype of the CD8+ T-cells in maternal spleen and lymph nodes that drain the uterus is not typical of activated, antigen-experienced T-cells suggesting that contact with fetal H-2Kb molecules induces a state of functional unresponsiveness.
Zhou
M
M
Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912-2600, USA.
Mellor
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AL
D000818:Animals; D001947:Breeding; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007112:Immunity, Maternally-Acquired; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011247:Pregnancy; D014327:Trophoblasts / Q000276:immunology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I