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

Abstract

Pregnancy manifests changes in the vascular and immune systems that persist postpartum (PP), have important implications for future pregnancies, and may modify responses to cardiovascular stress in late life. The association between immune and vascular function and the generation or progression of cardiovascular disease beg the question of whether altered immunity modifies pregnancy-induced changes in the vasculature. Our objective was to compare changes in the function and remodeling of systemic resistance vessels 4 weeks PP in normal C57BL/6 (B6), and immunodeficient mice recombinase 1-deficient/B6 (Rag1). Immune deficiency did not change the responsiveness to acetylcholine (ACh) and phenylephrine at baseline but decreased arterial distensibility and increased stiffness PP. Adoptive transfer of CD8 T cells into Rag1 À/À mice decreased the response to ACh while increasing distensibility and wall thickness. When compared to PP Rag1 À/À , vessels from PP CD4-deficient mice, which have B cells and CD8 T cells, but no CD4 cells, show increased distensibility and decreased responsiveness to ACh in a pattern similar to that seen in Rag1 À/À given CD8 T cells prior to mating. These studies suggest a key role for T cell, particularly CD8 T cell, associated factors in the PP remodeling of maternal resistance vessels.

Kinetics of Postpartum Mesenteric Artery Structure and Function Relative to Pregnancy and Lactation in Mice

“…In previous studies in rats, at 4 weeks PP, the reactivity of mesenteric vessels to vasoconstrictor (PE) or vasodilator (methacholine) was similar to those at pre-conception [ 42 ]. The findings reported herein and our previous observations [ 20 ] agree with these studies.…”

“…4a ). Moreover, arterial wall thickness increased and then decreased PP, consistent with our previous observations [ 20 ].…”

“…Previously, we demonstrated an increased distensibility and reduced arterial wall stiffness in the mesenteric vasculature of 4-week PP mice [ 20 ]. In this study, we specifically focused on maternal mesenteric vasculature.…”

Immune Cells in the Uterine Remodeling: Are They the Target of Endocrine Disrupting Chemicals?

“…Altogether, it is tempting to speculate that the participation of Tregs and probably of other adaptive cells rely on their interaction with other cell types. An interesting study from 2017 points out that CD8 + T cell reconstitution in recombinase 1-deficient mice (Rag −/− , without T and B cells) before mating abrogates the resistance differences in vasculature that normally persist postpartum (98). Thus, adaptive immune cells overtake unsuspected roles during pregnancy that go beyond their classical function.…”

In the Spotlight

“…In the current issue, Bonney and colleagues explore this topic by comparing changes in function and remodeling of systemic resistance vessels 4 weeks postpartum in normal C57BL/6 (B6) and immune-deficient mice, the recombinase 1-deficient/B6 (Rag1 À/À ), which have genetic absence of T and B cells, but have natural killer T cells, in order to focus on the critical role of the adaptive immunity. 12 Their results show that immune deficiency did not change responsiveness to acetylcholine (ACh) and phenylephrine at baseline but decreased arterial distensibility and increased stiffness postpartum. Adoptive transfer of CD8 T cells into Rag1 À/À mice decreased response to ACh while increasing distensibility and wall thickness.…”