Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8+ T-cell priming and viral control

2016 ◽  
Vol 54 (12) ◽  
pp. 1343-1404
Author(s):  
V Duhan ◽  
V Khairnar ◽  
SK Friedrich ◽  
C Hardt ◽  
PA Lang ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Replication ◽  
Marginal Zone ◽  
Cd8 T Cell ◽  
Viral Control ◽  
Specific Antibodies ◽  
T Cell Priming

scholarly journals Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8+ T-cell priming and viral control

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Vikas Duhan ◽  
Vishal Khairnar ◽  
Sarah-Kim Friedrich ◽  
Fan Zhou ◽  
Asmae Gassa ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Replication ◽  
Marginal Zone ◽  
Cd8 T Cell ◽  
Viral Control ◽  
Specific Antibodies ◽  
T Cell Priming

scholarly journals Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication

2016 ◽  
Vol 213 (13) ◽  
pp. 2913-2929 ◽  
Author(s):  
Shahzada Khan ◽  
Erik M. Woodruff ◽  
Martin Trapecar ◽  
Krystal A. Fontaine ◽  
Ashley Ezaki ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Replication ◽  
T Cell Activation ◽  
Cell Activation ◽  
Rna Viruses ◽  
Sexual Transmission ◽  
Cd8 T Cell ◽  
Female Reproductive Tract ◽  
Vaginal Mucosa ◽  
Viral Control

Understanding the host immune response to vaginal exposure to RNA viruses is required to combat sexual transmission of this class of pathogens. In this study, using lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) in wild-type mice, we show that these viruses replicate in the vaginal mucosa with minimal induction of antiviral interferon and inflammatory response, causing dampened innate-mediated control of viral replication and a failure to mature local antigen-presenting cells (APCs). Enhancement of innate-mediated inflammation in the vaginal mucosa rescues this phenotype and completely inhibits ZIKV replication. To gain a better understanding of how this dampened innate immune activation in the lower female reproductive tract may also affect adaptive immunity, we modeled CD8 T cell responses using vaginal LCMV infection. We show that the lack of APC maturation in the vaginal mucosa leads to a delay in CD8 T cell activation in the draining lymph node and hinders the timely appearance of effector CD8 T cells in vaginal mucosa, thus further delaying viral control in this tissue. Our study demonstrates that vaginal tissue is exceptionally vulnerable to infection by RNA viruses and provides a conceptual framework for the male to female sexual transmission observed during ZIKV infection.

scholarly journals Characterization of human cytomegalovirus peptide–specific CD8+ T-cell repertoire diversity following in vitro restimulation by antigen-pulsed dendritic cells

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 213-223 ◽  
Author(s):  
Karl Peggs ◽  
Stephanie Verfuerth ◽  
Arnold Pizzey ◽  
Jenni Ainsworth ◽  
Paul Moss ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Viral Replication ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Repertoire Diversity ◽  
Clonal Composition

Under conditions of impaired T-cell immunity, human cytomegalovirus (HCMV) can reactivate from lifelong latency, resulting in potentially fatal disease. A crucial role for CD8+ T cells has been demonstrated in control of viral replication, and high levels of HCMV-specific cytotoxic T-lymphocytes are seen in immunocompetent HCMV-seropositive individuals despite very low viral loads. Elucidation of the minimum portion of the anti-HCMV T-cell repertoire that is required to suppress viral replication requires further study of clonal composition. The ability of dendritic cells to take up and process exogenous viral antigen by constitutive macropinocytosis was used to study HCMV-specific T-cell memory in the absence of viral replication. The specificity and clonal composition of the CD8+ T-cell responses were evaluated using HLA tetrameric complexes and T-cell receptor β chain (TCRBV) spectratypic analyses. There was a skewed reactivity toward the matrix protein pp65, with up to 40-fold expansion of CD8+ T cells directed toward a single peptide-MHC combination. Individual expansions detected on TCRBV spectratype analysis were HCMV-specific and composed of single or highly restricted numbers of clones. There was preferential TCRBV gene usage (BV6.1/6.2, BV8, and BV13 in HLA-A*0201+ individuals) but lack of conservation of CDR3 length and junctional motifs between donors. While there was a spectrum of TCR repertoire diversity directed toward individual MHC-peptide combinations between donors, a relatively small number of clones appeared to predominate the response in each case. These data provide further insight into the range of anti-HCMV responses and will aid the design and monitoring of adoptive immunotherapy protocols.

scholarly journals Human conventional CD1c+ Dendritic Cells produce IL-12 and induce potent CD8+ T cell priming

2013 ◽  
Vol 4 ◽  
Author(s):  
Nizzoli Giulia ◽  
Weick Anja ◽  
Krietsch Jana ◽  
Steinfelder Svenja ◽  
Facciotti Federica ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Priming
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