Role for NKG2-A and NKG2-C surface receptors in chronic CD4+ T-cell responses.
Unidad de Inmunología, Facultad de Medicina, Servicio de Inmunología Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
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.
PMID: 15550116 [PubMed - indexed for MEDLINE]