Resistance of Extrathymic T Cells to Stress and the Role of Endogenous Glucocorticoids in Stress Associated Immuno Suppression

Abstract

When mice were exposed to restraint stress for 12 or 24 h, severe lymphopenia was induced in all immune system organs, including the liver and the thymus. However, in adrenalectomized mice, this response was completely absent. Phenotypic characterization revealed that interleukin (IL)-2Rbeta+CD3int cells (i.e. extrathymic T cells) with CD4+ phenotype and the NK1.1+ subset of CD3int cells (i.e. NKT cells) in the liver as well as the mature conventional T cells in the thymus were resistant to such stress. In adrenalectomized mice, there was no significant change in the distribution of lymphocyte subsets in all tested organs before stress. Interestingly, the number of lymphocytes in the liver and spleen and the proportion of NKT cells in the liver rather increased after stress in these adrenalectomized mice. Therefore, endogenous steroid hormones were indicated to be important in the induction of immunosuppressive states after stress. Among stress associated cytokines, the secretion of tumour necrosis factor (TNF)-alpha was completely suppressed while that of IL-6 was partially suppressed in adrenalectomized mice. These results suggest that endogenous steroid hormones are important for the induction of the stress associated immunosuppression and that NKT cells are resistant to stress, namely, resistant to exposure to endogenous steroid hormones.

Acute stress augments innate immunity in the liver and increases hyaluronan levels in the tissues and blood of mice

“…In the earlier studies, we have investigated the effect of long-term physical stress for 24 h on immunological conditions and found that the stress increased the concentration of catecholamines and corticosterone in the peripheral blood and that the stress changed the proportions of lymphocyte subsets in various tissues (28,30,32). Especially in liver, the percentages of IL-2Rβ…”

“…The expression of hyaluronan binding protein (HABP) was found to increase in the skin, liver and kidney as shown by immunohistochemical staining. An increase of HA in sera due to stress was seen at 3 h. The present results suggest that the activation of CD44 + T cells and unconventional T cells (i.e., innate immunity) in the blood and the elevated levels of HA (ligand for CD44) in the tissues and blood are crucial responses to acute stress exposure.There have been many reports on the relationship between various stresses and immunological conditions in humans, rats, and mice (4,6,28,30,32,38). Not only physical stress (21,22,28,30,32) but also psychological and psychosocial stress (3,4,8,14,19,38) increases the concentrations of catecholamines (i.e., adrenalin, noradrenalin, and dopamine) in the peripheral blood, resulting in a change in the number of lymphocytes (4,6,8,12,19,20,22,23).…”

“…Not only physical stress (21,22,28,30,32) but also psychological and psychosocial stress (3,4,8,14,19,38) increases the concentrations of catecholamines (i.e., adrenalin, noradrenalin, and dopamine) in the peripheral blood, resulting in a change in the number of lymphocytes (4,6,8,12,19,20,22,23). As for the clinical importance of stress, acute stress activates inflammation and improves wound healing, vaccination effectiveness and resistance to infection (7,9,10,38), while chronic stress is immunosuppressive (25) and impairs wound healing (11, 29).In the earlier studies, we have investigated the effect of long-term physical stress for 24 h on immunological conditions and found that the stress increased the concentration of catecholamines and corticosterone in the peripheral blood and that the stress changed the proportions of lymphocyte subsets in various tissues (28,30,32). Especially in liver, the percentages of IL-2Rβ…”

μ-Opioid Receptor Mediates Chronic Restraint Stress-Induced Lymphocyte Apoptosis

“…Studies on laboratory animals, in which environmental stimuli, genetic background, and immune challenge can be controlled, can potentially provide insight into the molecular and cellular processes that underlie the complex interactions among brain, behavior, and the immune system that influence pathogenic processes in humans. Numerous studies have revealed that adhesion molecules, various hormones (e.g., corticosteroids), and neurotransmitters (e.g., catecholamines) may be involved in stress-induced immune system changes, but the exact mechanisms by which stress affects the immune response have not been identified and characterized (10,11).…”

Evolution of Viral Hepatitis: Role of Psychosocial Stress

“…Restrain stress, another standardized method of assessing psychophysical stress in animal studies, was found to increase the proportion of NK cells in the mouse liver through increased HPA activity and higher than normal GC concentrations. (Shimizu et al, 2000) Recent studies shown that monocyte chemotactic protein (MCP 1) and macrophage inflammatory protein (MIP 2) distribute NK cells along with other chemokines, thus suggesting that GCs may influence this sub-population through down-regulation of these substances (Kawakami K et al, 2001;Faunce DE et al, 2000) Neutrophils are important in the early phases of hepatic inflammation. Circulating GCs have an inhibitory effect on neutrophil recruitment, as they down-regulate the expression of adhesion molecules, thus impairing chemotaxis.…”