Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus.
The human NKG2D killer lectin-like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3-kinase (PI3 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 well as TCRgammadelta(+) and TCRalphabeta(+)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 CD28(dull )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-gamma and TNF-alpha). 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.
Sáez-Borderías
Andrea
A
Molecular Immunopathology Unit, Universitat Pompeu Fabra (DCEXS), Barcelona, Spain.
Gumá
Mónica
M
Angulo
Ana
A
Bellosillo
Beatriz
B
Pende
Daniela
D
López-Botet
Miguel
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; C527054:KLRC1 protein, human; C527085:KLRK1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell