Murine T cell determination of pregnancy outcome.
At the fetomaternal interface, maternal effector cells come in intimate contact with fetal trophoblast cells which express paternal antigens. Failure of fetal trophoblast cells to activate maternal Th1 immune responses has been attributed in part to the absence of classical Class I and Class II major histocompatibilty complex (MHC) antigen expression and elaboration of factors which reduce TcR expression and shift any immune responses which may occur to Th2. Classical TcR alphabeta(+) T cells have not been found to be able to respond to trophoblasts. Recently, TcR gammadelta(+) T cells have been characterized in the low-abortion-rate pregnant C57Bl/10 mouse decidua, and the Vgamma1(+) subset may be able to respond to trophoblasts in a non-MHC-dependent manner. Trophoblast-recognizing T cells with Vgamma1 receptors are also present in the decidua of CBA/J mice pregnant by DBA/2, an abortion-prone mating combination. To test the role of the Vgamma1 subset of decidual gammadelta T cells in abortion-prone pregnancies, we altered this subset by injecting monoclonal anti-Vgamma1.1 antibody on gestation day 5.5, 1 day after implantation. This reduced detectability of a Vgammadelta subset producing TNF-alpha and reduced the abortion rate. Anti-Vgamma2, which reacts with a similar proportion of decidual gammadelta T cells as anti-Vgamma1.1, failed to prevent abortions. Vdelta6.3(+) cells are prominent at the fetomaternal interface, and anti-Vdelta6 antibody injected on day 5.5 prevented abortions. TGF-beta2(+) gammadelta cells first appear on day 8.5 of pregnancy; anti-Vgamma1.1 antibody injection on day 8.5 depleted these cells and boosted abortions; anti-Vdelta6.3 given on day 8.5 boosted abortions to the same level. These results suggest that two populations of Vgamma1.1(+)delta6.3(+) T cells may arise in the decidua: an early population that is Th1, abortogenic, and present during the time of implantation, and a Th2/3 cell subset that is present in the decidua later during pregnancy and which is pregnancy-protective.
Arck
P C
PC
Medizinische Fakultat der Humbolt, Universitat zu Berlin, Augustenburger Platz, Berlin, 13353, Germany.
Ferrick
D A
DA
Steele-Norwood
D
D
Egan
P J
PJ
Croitoru
K
K
Carding
S R
SR
Dietl
J
J
Clark
D A
DA
D000022:Abortion, Spontaneous / Q000209:etiology / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000633:toxicity; D003433:Crosses, Genetic; D016207:Cytokines / Q000502:physiology; D003656:Decidua / Q000276:immunology*; D005260:Female; D005327:Fetal Resorption / Q000276:immunology; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011248:Pregnancy Complications; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013312:Stress, Physiological / Q000150:complications; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D006183:H-2 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta