Social Defeat Modulates T Helper Cell Percentages in Stress Susceptible and Resilient Mice

Abstract

Altered adaptive immunity involving T lymphocytes has been found in depressed patients and in stress-induced depression-like behavior in animal models. Peripheral T cells play important roles in homeostasis and function of the central nervous system and thus modulate behavior. However, the T cell phenotype and function associated with susceptibility and resilience to depression remain largely unknown. Here, we characterized splenic T cells in susceptible and resilient mice after 10 days of social defeat stress (SDS). We found equally decreased T cell frequencies and comparably altered expression levels of genes associated with T helper (Th) cell function in resilient and susceptible mice. Interleukin (IL)-17 producing CD4+ and CD8+ T cell numbers in the spleen were significantly increased in susceptible mice. These animals further exhibited significantly reduced numbers of regulatory T cells (Treg) and decreased gene expression levels of TGF-β. Mice with enhanced Th17 differentiation induced by conditional deletion of PPARγ in CD4+ cells (CD4-PPARγKO), an inhibitor of Th17 development, were equally susceptible to SDS when compared to CD4-PPARγWT controls. These data indicate that enhanced Th17 differentiation alone does not alter stress vulnerability. Thus, SDS promotes Th17 cell and suppresses Treg cell differentiation predominantly in susceptible mice with yet unknown effects in immune responses after stress exposure.

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

“…Specifically, mesenteric lymph node cells from mice exposed to chronic circadian misalignment show increased differentiation of IL-17A + Th17 cells (Inokawa et al, 2020). Although effects of acute SD on adaptive immunity are not well characterized, exposure of male C57BL/6J mice to repeated SD by a larger, dominant male CD1 mouse results in increases in splenic IL-17-producing CD4 + and CD8 + T cells and reduced Treg in stress-susceptible mice, relative to control mice, as defined by the social interaction ratio in a social interaction test (Ambrée et al, 2019). These data are in turn consistent with previous studies demonstrating that development of learned helplessness in mice is dependent on increased Th17 responses, through RORγt-and IL-17A-dependent mechanisms (Beurel et al, 2013).…”

Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

“…[ 100 ] For instance, CSDS (which tends to be immunosuppressive) is characterized by a specific pattern of peripheral T cell responses associated with social defeat. [ 101 ]…”

Molecular Psychiatry: Trends and Study Examples

“…Finally, the article by Ambrée et al examining mechanistic aspects of the T cell response in stress-induced depression-like behavior [7] is outlined in the next section on animal models in more detail.…”

“…Ambrée and colleagues used social defeat stress (SDS) as a model for stress-induced depression-like behavior to shed light on the T cell phenotype associated with susceptibility and resilience to depression [7]. The authors grouped SDS-exposed mice into susceptible and resilient and found significantly increased numbers of interleukin-17 producing CD4+ and CD8+ T cells in the spleen of susceptible mice.…”

“…However, this genetic manipulation did not change susceptibility to SDS. Thus, while SDS promotes Th17 cell and suppresses Treg cell differentiation predominantly in susceptible mice, the effects in immune responses after stress exposure remain to be elucidated [7].…”