The H‐Y Response in Mid‐Gestation and Long After Delivery in Mice Primed Before Pregnancy

Abstract

The mechanisms underlying maternal tolerance of the semi-allogeneic fetus are not completely understood. The maternal immune system's response to the male antigen, H-Y is an example of the conflicting evidence that both supports and refutes the idea that the immune system in pregnant females is fundamentally different from that in non-pregnant females. Although multiple pregnancies may inactivate H-Y specific T cells, the immune system of the pregnant female can also generate a cytotoxic response to this antigen. To help understand this apparent conflict, we immunized female mice against H-Y with male spleen cells before pregnancy and examined the subsequent anti H-Y response during mid-pregnancy. The pregnant mice studied were able to mount cytotoxic immune responses to H-Y that were equivalent to those generated in their non-pregnant counterparts. Moreover the experience of pregnancy did not impair the ability to maintain immunologic memory to H-Y. The data support the idea that pregnancy does not violate general rules of antigen specific immunity, even if the antigen is expressed on the fetus.

PD-1 Regulates T Cell Proliferation in a Tissue and Subset-Specific Manner During Normal Mouse Pregnancy

“…Our studies here and elsewhere (Norton et al, 2009; Norton et al, 2010) suggest that T cells in the pregnant host, as in the non pregnant state, respond to signals leading to homeostatic proliferation, thus potentially rendering them susceptible to exhaustion and relief from exhaustion as further mechanisms of control. Examination of the intricacies of T cell regulation is likely to continue to reveal basic similarity between T cells in the pregnant and non pregnant host and enhance our understanding of how the pregnant immune system is capable of making an immune response leading to clearance of infections (Constantin et al, 2007), damaged tissue (Chaouat et al, 1995) and circulating fetal antigens (Bonney and Onyekwuluje, 2003) while supporting successful pregnancy.…”

Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice

“…62 Activated CD8 T cells contribute to the cytotoxic responses that can clear circulating fetal antigen 39 and support antiviral immunity during pregnancy. 25 CD8 T cells can also respond to vascular components 43,44 and may play a role in reactivity to vasoconstrictors or vasodilators 45 and in the development of hypertension and cardiovascular disease.…”

“…The CD8 T cells can respond to fetal antigens during pregnancy [39][40][41] and their phenotype is influenced by multiparty. 42 In addition, CD8 T cells exist that are specific for vascular endothelial growth factor, 43 and other vascular components 44 play a role in reactivity to vasoconstrictors or vasodilators 45 and influence the development of hypertension and cardiovascular disease.…”

Immune Regulation in Pregnancy

“…CD8 T cells are present at the maternal-fetal interface 104 , particularly during viral infection 24 . While CD8 T cells and be modified by pregnancy, they still can attack fetal cells in the maternal blood and lymphoid organs 105, 106 . In contrast, and adding to the paradigm that T reg support maternal tolerance, is the observation that pregnancy can support the generation of CD8 T reg 99, 107 , which may modify CD8 T cell cytotoxicity during pregnancy.…”

“…On a population level, memory T cells arise from a linearly differentiated subset of antigen specific T cells 108 . Pregnancy generates a pool of memory T cells that are specific for fetal antigen 4, 105 . Moreover, evidence suggests that vaccination or infection during pregnancy does not impair immunologic memory 24, 109 .…”