Attenuation of the cytotoxic T lymphocyte response to lymphocytic choriomeningitis virus in mice subjected to chronic social stress.
Chronic stress is suspected to increase the susceptibility to infections but experimental evidence from physiological stress models is scarce. We examined the effects of chronic social stress on virus-specific CTL responses in mice after infection with lymphocytic choriomeningitis virus (LCMV). Mice subjected to social stress on six consecutive days prior to infection showed a significant reduction of IFN-γ producing T(CD8+) splenocytes and markedly lowered plasma concentrations of IFN-γ. In contrast, the generation of LCMV-specific CTL responses was not altered in mice undergoing the same stress procedure concurrently with infection. Furthermore, stress exposure 6 days before and additional 3 days after LCMV infection profoundly reduced the expansion of T(CD8+) cells in the spleen, due to diminished in vivo proliferation. Pharmacological blockade of glucocorticoid receptors completely abrogated the stress-associated decline of T(CD8+) expansion. Stressed mice showed a significantly reduced expression of the early T-cell activation marker CD69 as well as impaired in vitro cytokine secretion of IFN-γ and IL-2. Additionally, social stress led to an altered migration capacity of T(CD8+) cells as demonstrated by adoptive T cell transfer experiments. Taken together, this study shows that chronic social stress fundamentally suppresses the functional capacities of T cells during a viral infection.
Division of Immunology, Department of Biology, Constance University, D-78457 Konstanz, Germany. Annette.Sommershof@uni-konstanz.de
Annette
A
Sommershof
Michael
M
Basler
Carsten
C
Riether
Harald
H
Engler
Marcus
M
Groettrup
D019264:Adoptive Transfer; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000963:Antimetabolites; D001284:Atrophy; D001973:Bromodeoxyuridine; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046988:Proteasome Endopeptidase Complex / Q000302:isolation & purification / Q000378:metabolism; D012931:Social Environment; D013315:Stress, Psychological / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D013950:Thymus Gland / Q000473:pathology
D000963:Antimetabolites; D006727:Hormone Antagonists; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex; D001973:Bromodeoxyuridine