Strong and durable TCR clustering at the T/dendritic cell immune synapse is not required for NFAT activation and IFN-gamma production in human CD4+ T cells.
The exact function of TCR clustering and organized macromolecular patterns at the immune synapse between APCs and T lymphocytes is unclear. Using human immature or mature dendritic cells (DCs) and autologous CD4(+) effector T cells, we demonstrate that, within a given conjugate, mature DCs induce strong and long-lasting TCR clustering and protein kinase C-theta translocation in a superantigen dose-dependent manner. Moreover, mature DCs promote CD43 exclusion in a dose-independent manner. In contrast, immature DCs are less potent at inducing these molecular rearrangements. Using these models to correlate T cell functions with the frequency, the intensity, and the duration of TCR clustering, we show, in Jurkat T cells, that weak and transient TCR clustering is sufficient to promote TCR down-modulation, protein kinase C-theta translocation at the synapse, and substantial NFAT transcriptional activation. Moreover, we show, in CD4(+) T cell blasts, that strong TCR clustering is required for neither TCR down-modulation nor optimal IFN-gamma production. Together, our results demonstrate that some CD4(+) functional responses, such as cytokine production, are independent of central supramolecular activation cluster formation.
Blanchard
Nicolas
N
Institut National de la Santé et de la Recherche Médicale, Unité 520, Institut Curie, Paris, France.
Decraene
Maud
M
Yang
Kun
K
Miro-Mur
Francesc
F
Amigorena
Sebastian
S
Hivroz
Claire
C
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010641:Phenotype; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D000074121:Protein Kinase C-theta; D021381:Protein Transport / Q000276:immunology / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D007371:Interferon-gamma; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta