Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes
Kugler DG, Flomerfelt FA, Costa DL, Laky K, Kamenyeva O, Mittelstadt PR, Gress RE, Rosshart SP, Rehermann B, Ashwell JD, Sher A, Jankovic D (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 213
Pages Range: 3041-3056
Journal Issue: 13
DOI: 10.1084/jem.20151636
Abstract
Because antigen-stimulated naive T cells either die as effectors or enter the activated/memory pool, continuous egress of new T lymphocytes from thymus is essential for maintenance of peripheral immune homeostasis. Unexpectedly, we found that systemic infection with the protozoan Toxoplasma gondii triggers not only a transient increase in activated CD4+ Th1 cells but also a persistent decrease in the size of the naive CD4+ T lymphocyte pool. This immune defect is associated with decreased thymic output and parasite-induced destruction of the thymic epithelium, as well as disruption of the overall architecture of that primary lymphoid organ. Importantly, the resulting quantitative and qualitative deficiency in naive CD4+ T cells leads to an immunocompromised state that both promotes chronic toxoplasma infection and leads to decreased resistance to challenge with an unrelated pathogen. These findings reveal that systemic infectious agents, such as T. gondii, can induce long-term immune alterations associated with impaired thymic function. When accumulated during the lifetime of the host, such events, even when occurring at low magnitude, could be a contributing factor in immunological senescence.
Authors with CRIS profile
Involved external institutions
US National Institutes of Health (NIH)
United States (USA) (US)
National Cancer Institute (NCI)
United States (USA) (US)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK / NIDDKD)
United States (USA) (US)
United States (USA) (US)
National Cancer Institute (NCI)
United States (USA) (US)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK / NIDDKD)
United States (USA) (US)
How to cite
APA:
Kugler, D.G., Flomerfelt, F.A., Costa, D.L., Laky, K., Kamenyeva, O., Mittelstadt, P.R.,... Jankovic, D. (2016). Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes. Journal of Experimental Medicine, 213(13), 3041-3056. https://dx.doi.org/10.1084/jem.20151636
MLA:
Kugler, David G., et al. "Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes." Journal of Experimental Medicine 213.13 (2016): 3041-3056.
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