Modulation of CD1d-restricted NKT cell responses by CD4

X Chen, X Wang, Gurdyal Besra, JE Gumperz

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20 Citations (Scopus)


CD4+ and CD4- NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4+ NKT cell clones, indicating that CD4 is functionally active in these cells. CD4 blockade specifically inhibited cytokine secretion and proliferation of CD4+ NKT cell clones in response to CD1d+ APCs but did not affect cytotoxicity, suggesting that CD4 preferentially modulates some NKT cell functional responses and not others. Anti-CD4 mAb treatment inhibited NKT cell responses to both MHC class II(+) and MHC class II(-) APCs, indicating that its effect was not due to blocking CD4 binding to MHC class II molecules on APCs. The inhibitory effect of the anti-CD4 mAb also did not require recognition of CD1d by the NKT cell, since calcium flux was reduced in response to anti-CD3 mAb stimulation. Western blot analysis revealed that anti-CD4 treatment resulted in increased phosphorylation of an inhibitory site of p56(lck) (tyrosine 505). Thus, CD4 blockade interferes with the course of CD3-mediated signaling events in NKT cells. These results indicate that CD4 can contribute to NKT cell activation independently of the presence of a CD4-ligand on APCs and suggest that it preferentially modulates cytokine and proliferative responses.
Original languageEnglish
Pages (from-to)1455-1465
Number of pages11
JournalJournal of Leukocyte Biology
Issue number6
Early online date25 Jul 2007
Publication statusPublished - 25 Jul 2007


  • p56(lck)
  • cytotoxicity
  • CD3
  • TCR
  • costimulation
  • MHC class II


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