Expression of CD94 and NKG2 molecules on human CD4(+) T cells in response to CD3-mediated stimulation.
We investigated the ability of human peripheral CD4(+) cells to express CD94 and NKG2 molecules as a consequence of CD3-mediated activation. Using highly purified peripheral CD4(+) T cells, we found expression of both CD94 and NKG2A 15 days after CD3-mediated stimulation of cells. We also determined by reverse transcriptase-PCR that all gene members of NKG2 family-namely, NKG2A, -C, -D, and -E-are sequentially expressed on CD4(+) cells. We found that this expression is tightly regulated by cytokines, and we identified transforming growth factor-beta1 and interleukin-10 as the main factors that, on CD3-dependent stimulation, positively contribute to the expression of CD94 and NKG2A on CD4(+) cells. We also investigated the functional role of NKG2A and found that coligation of CD3 and NKG2A by specific monoclonal antibodies results in significant inhibition of interferon gamma and tumor necrosis factor alpha production by stimulated CD4(+) cells. The presence and function of these receptors on CD4(+) lymphocytes support a more general role for NKG2 molecules, whose functions were originally thought to be confined to cytotoxic cells, in the immune system.
Romero
P
P
Departamento de Inmunología, Facultad de Medicina, Hospital Universitario "Reina Sofía," Universidad de Córdoba, Córdoba, Spain.
Ortega
C
C
Palma
A
A
Molina
I J
IJ
Peña
J
J
Santamaría
M
M
D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D017252:CD3 Complex / Q000494:pharmacology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma