title: Systemic toxoplasma infection triggers a long-term defect in the generation and function of naive T lymphocytes.
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.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: David G
authors.initials: DG
authors.lastname: Kugler
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Francis A
authors.identifier: 0000-0003-3422-606X
authors.initials: FA
authors.lastname: Flomerfelt
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Diego L
authors.identifier: 0000-0002-9440-2814
authors.initials: DL
authors.lastname: Costa
authors.affiliation: T Cell Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Karen
authors.initials: K
authors.lastname: Laky
authors.affiliation: Biological Imaging, Research Technology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Olena
authors.identifier: 0000-0002-6541-5616
authors.initials: O
authors.lastname: Kamenyeva
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Paul R
authors.identifier: 0000-0003-3295-3052
authors.initials: PR
authors.lastname: Mittelstadt
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ronald E
authors.identifier: 0000-0001-8259-5332
authors.initials: RE
authors.lastname: Gress
authors.affiliation: Immunology Section, Liver Diseases Branch, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Stephan P
authors.identifier: 0000-0002-6989-8686
authors.initials: SP
authors.lastname: Rosshart
authors.affiliation: Immunology Section, Liver Diseases Branch, National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jonathan D
authors.identifier: 0000-0002-7386-8738
authors.initials: JD
authors.lastname: Ashwell
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 DJankovic@niaid.nih.gov ASher@niaid.nih.gov.
authors.forename: Alan
authors.identifier: 0000-0001-7053-2895
authors.initials: A
authors.lastname: Sher
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 DJankovic@niaid.nih.gov ASher@niaid.nih.gov.
authors.forename: Dragana
authors.identifier: 0000-0001-7360-1809
authors.initials: D
authors.lastname: Jankovic
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology