Research Article: Role for NKG2-A and NKG2-C surface receptors in chronic CD4 super(+) T-cell responses

• Published in: Immunology and cell biology 2004-12, Vol.82 (6), p.587-595
• Main Authors: Ortega, Consuelo, Romero, Pilar, Palma, Agustin, Orta, Teresa, Pena, Jose, Garcia-Vinuesa, Amaya, Molina, Ignacio J, Santamaria, Manuel
• Format: Article
• Language: English
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/j.0818-9641.2004.01284.x

The participation of CD94 and NKG2 gene family members in the function of NK cells and CD8 super(+) cytolytic cells has recently been addressed in detail. However, the role that these molecules play in the key CD4 super(+) regulatory cells remains largely unexplored. This study has examined the expression and regulation of CD94 and NKG2 genes in purified human peripheral CD4 super(+) cells stimulated with several agents. We found a constitutive expression of NKG2-E in CD94-depleted resting peripheral CD4 super(+) 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 super(+) T cells, where mRNA from all NKG2 gene family members are detected after 5 days of stimulation. Selective activation of TCR V beta sub(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 super(+) 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 super(+) cells that are different from those governing the expression of these same genes in CD8 super(+) cells. The results suggest that these genes also participate in chronic CD4 super(+) T-cell responses.