scholarly journals The HIV-1 Tat Protein Induces the Activation of CD8+ T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e77746 ◽  
Author(s):  
Francesco Nicoli ◽  
Valentina Finessi ◽  
Mariaconcetta Sicurella ◽  
Lara Rizzotto ◽  
Eleonora Gallerani ◽  
...  
2021 ◽  
Author(s):  
Marta Calvet-Mirabent ◽  
Daniel T. Claiborne ◽  
Maud Deruaz ◽  
Serah Tanno ◽  
Carla Serra ◽  
...  

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.


2002 ◽  
Vol 168 (5) ◽  
pp. 2111-2117 ◽  
Author(s):  
Shigeo Koido ◽  
Yasuhiro Tanaka ◽  
Dongshu Chen ◽  
Donald Kufe ◽  
Jianlin Gong

2008 ◽  
Vol 180 (11) ◽  
pp. 7230-7239 ◽  
Author(s):  
Elisabetta Parretta ◽  
Giuliana Cassese ◽  
Angela Santoni ◽  
John Guardiola ◽  
Antonia Vecchio ◽  
...  

Virology ◽  
2003 ◽  
Vol 305 (2) ◽  
pp. 339-352 ◽  
Author(s):  
Simon J. Potter ◽  
Dominic E. Dwyer ◽  
Nitin K. Saksena

2009 ◽  
Vol 83 (7) ◽  
pp. 2862-2871 ◽  
Author(s):  
Alexandre Harari ◽  
Felicitas Bellutti Enders ◽  
Cristina Cellerai ◽  
Pierre-Alexandre Bart ◽  
Giuseppe Pantaleo

ABSTRACT Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin− GrmB− GrmA+/− GrmK+; in CMV-specific cells, it was perforin+ GrmB+ GrmA+ GrmK−/+; and in EBV- and HIV-1-specific cells, it was perforin−/+ GrmB+ GrmA+ GrmK+. On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK+ profile was associated with early-stage memory CD8 T-cell differentiation, the perforin+ GrmB+ GrmA+ profile with advanced-stage differentiation, and the GrmB+ GrmA+ Grmk+ profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.


1999 ◽  
Vol 67 (8) ◽  
pp. 3980-3988 ◽  
Author(s):  
Natalya V. Serbina ◽  
JoAnne L. Flynn

ABSTRACT Several lines of evidence suggest that CD8 T cells are important in protection against tuberculosis. To understand the function of this cell population in the immune response against Mycobacterium tuberculosis, T cells from lungs of M. tuberculosis-infected mice were examined by flow cytometry. The kinetics of the appearance of CD8 T cells in lungs of infected mice closely paralleled that of CD4 T cells. Both CD4+ and CD8+ T cells displaying an activated phenotype were found in the lungs as early as 1 week postinfection. By 2 weeks, total cell numbers in the lungs had tripled and percentages of T cells were increased two- to threefold; the percentages of CD4+ T cells were ca. twofold higher than those of CD8+ T cells. Short-term stimulation with M. tuberculosis-infected antigen-presenting cells induced cytokine production by primed CD4+ and CD8+ T cells. Intracellular cytokine staining revealed that 30% ± 5% of CD4+ and 23% ± 4% of CD8+ T cells were primed for production of gamma interferon (IFN-γ). However, a difference in in vivo IFN-γ production by T cells was observed with ∼12% of CD4+ T cells and ∼5% of CD8+ T cells secreting cytokine in the lungs at any given time during infection. The data presented indicate that although early in infection the majority of IFN-γ is produced by CD4+ T cells, cytokine-producing CD8+ T cells are readily available when triggered by the appropriate stimuli.


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