Abstract
CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.
| Original language | English |
|---|---|
| Pages (from-to) | 1069-1081 |
| Number of pages | 13 |
| Journal | European Journal of Immunology |
| Volume | 45 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2015 |
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Keywords
- CD8 T lymphocytes
- HLA-E
- Mycobacterium tuberculosis
- TB
- Tetramers
- Type 2 cytokines
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines. / Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C.; Brooks, Andrew G.; Prezzemolo, Teresa; La Manna, Marco P.; Di liberto, Diana; Joosten, Simone A.; van Meijgaarden, Krista E.; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C.; Ottenhoff, Tom H M; Dieli, Francesco.
In: European Journal of Immunology, Vol. 45, No. 4, 01.04.2015, p. 1069-1081.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines
AU - Caccamo, Nadia
AU - Pietra, Gabriella
AU - Sullivan, Lucy C.
AU - Brooks, Andrew G.
AU - Prezzemolo, Teresa
AU - La Manna, Marco P.
AU - Di liberto, Diana
AU - Joosten, Simone A.
AU - van Meijgaarden, Krista E.
AU - Di Carlo, Paola
AU - Titone, Lucina
AU - Moretta, Lorenzo
AU - Mingari, Maria C.
AU - Ottenhoff, Tom H M
AU - Dieli, Francesco
PY - 2015/4/1
Y1 - 2015/4/1
N2 - CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.
AB - CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB.
KW - CD8 T lymphocytes
KW - HLA-E
KW - Mycobacterium tuberculosis
KW - TB
KW - Tetramers
KW - Type 2 cytokines
UR - http://www.scopus.com/inward/record.url?scp=84927071832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927071832&partnerID=8YFLogxK
U2 - 10.1002/eji.201445193
DO - 10.1002/eji.201445193
M3 - Article
C2 - 25631937
AN - SCOPUS:84927071832
VL - 45
SP - 1069
EP - 1081
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 4
ER -