ABSTRACT
Tissue-resident memory T cells (TRM cells) are a novel population of tissue-restricted antigen-specific T cells. TRM cells are induced by pathogens and promote host defense against secondary infections. Although TRM cells cannot be detected in circulation, they are the major memory CD4+ and CD8+ T-cell population in tissues in mice and humans. Murine models of CD8+ TRM cells have shown that CD8+ TRM cells maintain tissue residency via CD69 and though tumor growth factor ß-dependent induction of CD103. In contrast to CD8+ TRM cells, there are few models of CD4+ TRM cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4+ TRM cells. Citrobacter rodentium is known to induce IL-17+ and IL-22+ CD4+ T cells (Th17 and Th22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22+ cells in the colon 3 months after C. rodentium infection are CD4+ T cells. This collectively suggests that C. rodentium may induce CD4+ TRM cells. Here, we demonstrate that C. rodentium induces a population of IL-17A+ CD4+ T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4+ TRM cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T cells but not tissue-restricted T cells, we show that these CD4+ TRM cells can promote host defense.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Citrobacter rodentium/immunology , Enterobacteriaceae Infections/immunology , Animals , Citrobacter rodentium/genetics , Enterobacteriaceae Infections/genetics , Enterobacteriaceae Infections/microbiology , Humans , Immunologic Memory , Interleukin-17/genetics , Interleukin-17/immunology , Interleukins/genetics , Interleukins/immunology , Mice , Mice, Inbred C57BL , Th17 Cells/immunology , Interleukin-22ABSTRACT
F-18-fluoro-deoxy-glucose positron emission tomography (PET) is highly sensitive and specific in the imaging of B-cell lymphomas. In contrast, its utility in the diagnostic evaluation of T-cell lymphomas is less defined. In this article, we present our finding utilizing PET in peripheral T-cell lymphomas (PTCL). A retrospective review of patients who underwent PET examinations at our institution produced 24 PET examinations among patients with PTCL. A lesion-based analysis was undertaken to evaluate the diagnostic accuracy of PET in PTCL. PET findings were compared with a standard of reference and sensitivity, specificity, positive and negative predictive values were calculated. PET had an overall sensitivity of 86% and specificity of 100%. PET had high sensitivity (95%) at nodal and non-cutaneous extra-nodal sites and poor sensitivity (13%) at cutaneous sites. The mean SUV of abnormal foci in anaplastic large cell lymphoma was 11 mg/ml (range: 3 - 40), and PTCL-unclassified was 8 mg/ml (range: 1 - 23).
