scholarly journals T Cells Infiltrate the Brain in Murine and Human Transmissible Spongiform Encephalopathies

2003 ◽  
Vol 77 (6) ◽  
pp. 3799-3808 ◽  
Author(s):  
Hanna Lewicki ◽  
Antoinette Tishon ◽  
Dirk Homann ◽  
Honoré Mazarguil ◽  
Françoise Laval ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Class I ◽  
Transmissible Spongiform Encephalopathies ◽  
Activated T Cells ◽  
Necrosis Factor Alpha ◽  
Tetramer Binding ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP−/−) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1β, IFN-γ-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease. T cells harvested from brains and spleens of scrapie-infected mice were analyzed using a newly identified mouse PrP (mPrP) peptide bearing the canonical binding motifs to major histocompatibility complex (MHC) class I H-2b or H-2d molecules, appropriate MHC class I tetramers made to include these peptides, and CD4 and CD8 T cells stimulated with 15-mer overlapping peptides covering the whole mPrP. Minimal to modest Kb tetramer binding of mPrP amino acids (aa) 2 to 9, aa 152 to 160, and aa 232 to 241 was observed, but such tetramer-binding lymphocytes as well as CD4 and CD8 lymphocytes incubated with the full repertoire of mPrP peptides failed to synthesize intracellular gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) cytokines and were unable to lyse PrP−/− embryo fibroblasts or macrophages coated with 51Cr-labeled mPrP peptide. These results suggest that the expression of PrPsc in the CNS is associated with release of chemokines and, as shown previously, cytokines that attract and retain PrP-activated T cells and, quite likely, bystander activated T cells that have migrated from the periphery into the CNS. However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-γ and TNF-α expression or release or lytic activity.

scholarly journals Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells

2002 ◽  
Vol 195 (4) ◽  
pp. 473-483 ◽  
Author(s):  
Robbie B. Mailliard ◽  
Shinichi Egawa ◽  
Quan Cai ◽  
Anna Kalinska ◽  
Svetlana N. Bykovskaya ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Class I ◽  
Chronic Infections ◽  
Cd40 Ligation ◽  
Activation Level ◽  
Tnf Α ◽  
Ifn Γ

Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of “T helper (Th)” signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood– or peripheral blood–isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-γ at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I–presented epitopes by antigen-specific CD8+ T cells results in the TNF-α– and IFN-γ–dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I–restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections.

scholarly journals Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination

2009 ◽  
Vol 17 (1) ◽  
pp. 118-126 ◽  
Author(s):  
Maria Luiza Silva ◽  
Luçandra Ramos Espírito-Santo ◽  
Marina Angela Martins ◽  
Denise Silveira-Lemos ◽  
Vanessa Peruhype-Magalhães ◽  
...  
Keyword(s):  
T Cells ◽  
B Lymphocytes ◽  
Yellow Fever ◽  
Ex Vivo ◽  
Present Report ◽  
Suspected Case ◽  
Activated T Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-γR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3+ CD16+/− CD56+/−/CD3+ ratio), activated T cells (CD4+ and CD8+ cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-γ+], tumor necrosis factor alpha positive [TNF-α+], and IL-4 positive [IL-4+]), CD8+ T cells (IL-4+ and IL-5+), and B lymphocytes (TNF-α+, IL-4+, and IL-10+). The analysis of CD4+ T cells revealed a complex profile that consisted of an increased frequency of IL-12+ and IFN-γ+ cells and a decreased percentage of TNF-α+, IL-4+, and IL-5+ cells. Depressed cytokine synthesis was observed in monocytes (TNF-α+) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.

scholarly journals Nef-mediated MHC class I down-regulation unmasks clonal differences in virus suppression by SIV-specific CD8+ T cells independent of IFN-γ and CD107a responses

Virology ◽  
2009 ◽  
Vol 391 (1) ◽  
pp. 130-139 ◽  
Author(s):  
Jacob T. Minang ◽  
Matthew T. Trivett ◽  
Lori V. Coren ◽  
Eugene V. Barsov ◽  
Michael Piatak ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Class I ◽  
Down Regulation ◽  
Ifn Γ ◽  
Virus Suppression

scholarly journals CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination

Gene Therapy ◽  
2003 ◽  
Vol 10 (16) ◽  
pp. 1311-1320 ◽  
Author(s):  
W F Cheng ◽  
C F Hung ◽  
K Y Lin ◽  
M Ling ◽  
J Juang ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Dna Vaccination ◽  
Class I ◽  
Ifn Γ

scholarly journals Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

2006 ◽  
Vol 75 (3) ◽  
pp. 1154-1166 ◽  
Author(s):  
Laura H. Hogan ◽  
Dominic O. Co ◽  
Jozsef Karman ◽  
Erika Heninger ◽  
M. Suresh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bacterial Load ◽  
Granulomatous Inflammation ◽  
Cd8 T Cell ◽  
Activated T Cells ◽  
Immunodeficient Mice ◽  
Ifn Γ

ABSTRACT The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.

Role of MHC class I and CD8+ T cells in the pathogenesis of chronic rejection

2001 ◽  
Vol 33 (1-2) ◽  
pp. 319 ◽  
Author(s):  
H Sun ◽  
V Subbotin ◽  
J Woodward ◽  
L Valdivia ◽  
J.J Fung ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Chronic Rejection ◽  
Class I
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