Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes

作者：Kugler David G; Flomerfelt Francis A; Costa Diego L; Laky Karen; Kamenyeva Olena; Mittelstadt Paul R; Gress Ronald E; Rosshart Stephan P; Rehermann Barbara; Ashwell Jonathan D; Sher Alan; Jankovic Dragana

来源：Journal of Experimental Medicine, 2016, 213(13): 3041-3056.

DOI：10.1084/jem.20151636

<jats:p>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 <jats:italic>Toxoplasma
gondii</jats:italic> triggers not only a transient increase in activated
CD4<jats:sup>+</jats:sup> Th1 cells but also a persistent decrease in the size of the
naive CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> 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 <jats:italic>T. gondii</jats:italic>, 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.</jats:p>

• 出版日期2016-12
• 单位National Institutes of Health; National Cancer Institute