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Th17 Lymphocytes (th17 + lymphocyte)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Preferential recruitment of interferon-,,expressing TH17 cells in multiple sclerosis,

ANNALS OF NEUROLOGY, Issue 3 2009
Hania Kebir MSc
Objective There is substantial evidence supporting the role of interferon (IFN)-,,producing T helper (TH) 1 and interleukin (IL)-17,expressing TH17 lymphocytes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). However, to date little is known about the potential cooperative interplay between these 2 cytokines. In the current study, we sought to evaluate the frequency of IFN-,,expressing TH17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS). Methods Human TH17 lymphocytes were expanded in vitro from the blood of healthy controls and relapsing MS patients using IL-23. Immune cell migration to the CNS was assessed in vitro with primary cultures of human blood,brain barrier (BBB)-derived endothelial cells, and in vivo in EAE mice. Results We demonstrate that in response to IL-23, human memory lymphocytes expand into a TH17 phenotype, with a subpopulation of cells simultaneously expressing IFN-, and IL-17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN-,,producing TH17 cells and identify numerous T lymphocytes coexpressing IL-17 and IFN-, in brain tissue of MS patients. We also find lymphocytes expressing both the TH1- and the TH17-associated transcription factors ROR,t and T-bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN-,+ TH17 lymphocytes preferentially cross the human BBB and accumulate in the CNS of mice during the effector phase of EAE. Interpretation Our data underscore the involvement of IFN-,+ TH17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events. Ann Neurol 2009;66:390,402 [source]

CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2010
Laura Maggi
Abstract We have previously shown that human Th17 lymphocytes are characterized by the selective expression of IL-23 receptor (IL-23R), CCR6, CD161, and the transcription factor retinoic acid-related orphan receptor C (RORC), and originate from a CD161+CD4+ naïve T-cell precursor in response to the combined activity of IL-1, and IL-23. We show here that not only CD4+TCR,,+, but also CD8+TCR,,+, CD4,CD8, TCR,,+, and CD4,CD8, TCR,,+ circulating lymphocytes that produce IL-17 express the distinctive marker CD161 on their surface. In addition, we demonstrate that CD161 expression identifies CD8+ and CD4,CD8, umbilical cord blood T cells that already express RORC and IL-23R mRNA and that can be induced to differentiate into IL-17-producing cells in the presence of IL-1, and IL-23. Finally, we provide evidence that umbilical cord blood naïve CD4+CD161, T cells, upon lentivirus-mediated transduction with RORC2 can acquire the ability to express IL-23R, IL-1RI, and CD161, as well as to produce IL-17. Taken together, these data allow to conclude that T-cell subsets able to produce IL-17, as well as precursors of IL-17-producing T cells, exhibit surface expression of CD161, and that this feature is at least in part RORC2-dependent. [source]

T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-,,

ANNALS OF NEUROLOGY, Issue 5 2009
Luca Durelli MD
Objective T-helper 1 (Th1) and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression sensitivity to IFN-, in MS patients. Methods In 30 untreated patients with active MS (AMS) and 32 with inactive MS (IMS), and in 22 healthy subjects, we measured intracellular cytokine expression, interleukin-17,producing myelin basic protein,stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-,R1) expression, IFN-,-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation, and apoptosis of anti-CD3 monoclonal antibody,stimulated PB lymphocytes. Results Th17 cell percentage increased around sevenfold in AMS compared with IMS or healthy subjects, but there was no change in Th1 cells. Th17 cells in AMS were myelin basic protein specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-,R1 expression, IFN-,,induced STAT1 activation, and apoptosis were significantly greater in Th17 than Th1 cells. IFN-,R1 expression and IFN-,,dependent STAT1 activation progressively increased in vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells. Interpretation Evidence that an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, is associated with disease activity in MS. The greater IFN-,R1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-, therapy. Ann Neurol 2009;65:499,509 [source]

Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues

ARTHRITIS & RHEUMATISM, Issue 7 2010
Mohammed F. Shamji
Objective Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. Methods Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. Results Immunoreactivity for IL-4, IL-6, IL-12, and interferon-, (IFN,) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. Conclusion Greater IFN, positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration. [source]