Role for NKG2-A and NKG2-C surface receptors in chronic CD4+ T-cell responses.
The participation of CD94 and NKG2 gene family members in the function of NK cells and CD8+ cytolytic cells has recently been addressed in detail. However, the role that these molecules play in the key CD4+ regulatory cells remains largely unexplored. This study has examined the expression and regulation of CD94 and NKG2 genes in purified human peripheral CD4+ cells stimulated with several agents. We found a constitutive expression of NKG2-E in CD94-depleted resting peripheral CD4+ cells, whereas inductions of NKG2-A and NKG2-C required chronic cell activation and occurred after expression of CD94. We found that CD3-mediated stimulation induces the expression of CD94 first by day 5 of culture, followed by NKG2-A by day 15 and finally NKG2-C, which is not detected until 20 days after repeated stimulation. This pattern of gene expression differs sharply from that observed in purified CD8+ T cells, where mRNA from all NKG2 gene family members are detected after 5 days of stimulation. Selective activation of TCR V beta 2-bearing cells with toxic shock syndrome toxin-1 superantigen reveals that mRNA induction of NKG2-A and NKG2-C genes is significantly influenced by the presence of cytokines (IL-10 and TGF-beta) and by the restimulation of the cells. In addition, the occupancy of the CD94/NKG2-A receptor expressed on these superantigen-stimulated CD4+ T lymphocytes abrogates TNF-alpha and IFN-gamma production, whereas NKG2-C enhances production of these cytokines. Taken together our results reveal strict gene regulatory mechanisms for CD94 and NKG2 gene expression on CD4+ cells that are different from those governing the expression of these same genes in CD8+ cells. The results suggest that these genes also participate in chronic CD4+ T-cell responses.
Ortega
Consuelo
C
Unidad de Inmunología, Facultad de Medicina, Servicio de Inmunología Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
Romero
Pilar
P
Palma
Agustín
A
Orta
Teresa
T
Peña
José
J
García-Vinuesa
Amaya
A
Molina
Ignacio J
IJ
Santamaría
Manuel
M
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D016853:Muromonab-CD3 / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D018089:Superantigens / Q000276:immunology; D013997:Time Factors
D015703:Antigens, CD; D016207:Cytokines; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C527062:KLRC3 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D016853:Muromonab-CD3; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018089:Superantigens