Analysis of the global CD8 T cells during Mycobacterium tuberculosis infection.
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1
DIBIMEF, University of Palermo, Italy
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2
DIMES-Università degli studi di Genova, Italy
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3
Department od Microbiology and Immunology, University of Melbourne, Australia
Tuberculosis is a world-wide re-emerging infectious disease caused by Mycobacterium tuberculosis (Mtb) and both BCG vaccine and therapy are not fully effective in containing its spreading.
We investigated the frequency of Mtb epitope-specific HLA-E-restricted CD8 T cells in adult patients affected by tuberculosis (TB) before and after 6 months of anti-mycobacterial therapy and in healthy subjects. Using peptides/HLA-E tetramers, we found a high frequency of peptide-specific CD8 T cells in peripheral blood of patients with active TB, which consistently decrease after therapy. HLA-E-specific T cells produced in vitro high levels TNF, but very poor IFN-gamma and/or IL-2 and exerted cytotoxic activities toward peptide-pulsed HLA-E transfected target cells. Monitoring of epitope-specific HLA-E-restricted CD8 T cells by the use of tetramers in PBMC of Mtb patients during chemotherapeutic treatment, showed their frequency decreased, a pattern opposite to HLA-A*0201-restricted CD8 T cells, whose frequency instead increased after therapy. Our results indicate that HLA-E-restricted CD8 T cells behave and function differently than HLA-A-restricted CD8 T cells and could be an useful parameter to check the efficacy of therapy.
Moreover, since HLA-E is an highly conserved molecule with a very limited polymorphism and it’s not down-regulated by HIV infection, often associated to TB reactivation, the evaluation of ex-vivo frequencies of peptides-specific HLA-E CD8 T cells could be useful to predict subjects that are at high risk to develop the disease and these peptides could be suitable candidates for a more effective vaccine against Mtb in HIV subjects.
Keywords:
Mycobacterium tuberculosis,
HLA-E tetramers,
Cytokines,
TB patients,
CD8 T cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Host-pathogen interactions
Citation:
Di Liberto
D,
La Manna
M,
Caccamo
N,
Pietra
G,
Mingari
C,
Sullivan
L,
Brooks
A and
Dieli
F
(2013). Analysis of the global CD8 T cells during Mycobacterium tuberculosis infection..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00723
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Received:
17 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Diana Di Liberto, DIBIMEF, University of Palermo, Palermo, Italy, diana.diliberto@unipa.it