TY - JOUR
T1 - Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus
AU - Sáez-Borderías, Andrea
AU - Gumá, Mónica
AU - Angulo, Ana
AU - Bellosillo, Beatriz
AU - Pende, Daniela
AU - López-Botet, Miguel
PY - 2006/12
Y1 - 2006/12
N2 - The human NKG2D killer lectin-like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3-kinase (P13 K) and specifically interacts with different stress-inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus-infected cells. This KLR is commonly expressed by human NK cells as wen as TCRγδ + and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)-specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28- and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR-dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN-γ and TNF-α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV-specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.
AB - The human NKG2D killer lectin-like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3-kinase (P13 K) and specifically interacts with different stress-inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus-infected cells. This KLR is commonly expressed by human NK cells as wen as TCRγδ + and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)-specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28- and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR-dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN-γ and TNF-α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV-specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.
KW - Cytomegalovirus
KW - GD85j
KW - KIR
KW - NKG2D
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=33845593312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845593312&partnerID=8YFLogxK
U2 - 10.1002/eji.200636682
DO - 10.1002/eji.200636682
M3 - Article
C2 - 17109473
AN - SCOPUS:33845593312
VL - 36
SP - 3198
EP - 3206
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 12
ER -