CD1-dependent dendritic cell instruction


Both microbial products and T cell factors influence dendritic cell (DC) maturation. However, it is not known which T cells are capable of interacting with DCs at the initiation of adaptive immunity, when foreign antigen–specific T cells are rare. We show here that self-reactive CD1-restricted T cells can promote DC maturation by recognizing CD1 in the absence of foreign antigens. T cell recognition of all four CD1 isoforms can trigger DC maturation, but their distinct mechanisms of costimulation lead to profound differences in concomitant interleukin 12 p70 production. Distinct CD1-reactive T cells may thus differentially direct DC development early in the immune response, thereby controlling subsequent polarization of acquired immunity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: CD1-dependent DC maturation.
Figure 2: Inhibition of T cell–induced CD86 expression.
Figure 3: Differential cytokine production by DCs in the presence of LPS- and CD1-reactive T cells.
Figure 4: T cell polarization by DCs.
Figure 5: Factors that regulate IL-12 production by DCs.
Figure 6: Differential mechanisms for IL-12p70 production for CD1 self-reactive cells.


  1. 1

    Lanzavecchia, A. & Sallusto, F. Regulation of T cell immunity by dendritic cells. Cell 106, 263–266 (2001).

    CAS  Article  Google Scholar 

  2. 2

    Hilkens, C.M., Kalinski, P., de Boer, M. & Kapsenberg, M.L. Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype. Blood 90, 1920–1926 (1997).

    CAS  PubMed  Google Scholar 

  3. 3

    Schulz, O. et al. CD40 triggering of heterodimeric IL-12p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13, 453–462 (2000).

    CAS  Article  Google Scholar 

  4. 4

    Hawiger, D. et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194, 769–779 (2001).

    CAS  Article  Google Scholar 

  5. 5

    Kalinski, P., Schuitemaker, J.H., Hilkens, C.M., Wierenga, E.A. & Kapsenberg, M.L. Final maturation of dendritic cells is associated with impaired responsiveness to IFN-γ and to bacterial IL-12 inducers: decreased ability of mature dendritic cells to produce IL-12 during the interaction with Th cells. J. Immunol. 162, 3231–3236 (1999).

    CAS  PubMed  Google Scholar 

  6. 6

    Langenkamp, A., Messi, M., Lanzavecchia, A. & Sallusto, F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nature Immunol. 1, 311–316 (2000).

    CAS  Article  Google Scholar 

  7. 7

    Porcelli, S.A. & Modlin, R.L. The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu. Rev. Immunol. 17, 297–329 (1999).

    CAS  Article  Google Scholar 

  8. 8

    Benlagha, K. & Bendelac, A. CD1d-restricted mouse Vα14 and human Vα24 T cells: lymphocytes of innate immunity. Semin. Immunol. 12, 537–542 (2000).

    CAS  Article  Google Scholar 

  9. 9

    Beckman, E.M. et al. Recognition of a lipid antigen by CD1-restricted αβ+ T cells. Nature 372, 691–694 (1994).

    CAS  Article  Google Scholar 

  10. 10

    Sieling, P.A. et al. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269, 227–230 (1995).

    CAS  Article  Google Scholar 

  11. 11

    Moody, D.B. et al. Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science 278, 283–286 (1997).

    CAS  Article  Google Scholar 

  12. 12

    Shamshiev, A. et al. Self glycolipids as T-cell autoantigens. Eur. J. Immunol. 29, 1667–1675 (1999).

    CAS  Article  Google Scholar 

  13. 13

    Shamshiev, A. et al. Presentation of the same glycolipid by different CD1 molecules. J. Exp. Med. 195, 1013–1021 (2002).

    CAS  Article  Google Scholar 

  14. 14

    Exley, M., Garcia, J., Balk, S.P. & Porcelli, S. Requirements for CD1d recognition by human invariant Vα24+ CD4CD8 T cells. J. Exp. Med. 186, 109–120 (1997).

    CAS  Article  Google Scholar 

  15. 15

    Gumperz, J.E., Miyake, S., Yamamura, T. & Brenner, M.B. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J. Exp. Med. 195, 625–636 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Pierre, P. et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388, 787–792 (1997).

    CAS  Article  Google Scholar 

  17. 17

    Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp. Med. 179, 1109–1118 (1994).

    CAS  Article  Google Scholar 

  18. 18

    Caux, C. et al. Activation of human dendritic cells through CD40 cross-linking. J. Exp. Med. 180, 1263–1272 (1994).

    CAS  Article  Google Scholar 

  19. 19

    Anderson, D.M. et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390, 175–179 (1997).

    CAS  Article  Google Scholar 

  20. 20

    Rescigno, M. et al. Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1β, and the production of interferon γ in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses. J. Exp. Med. 192, 1661–1668 (2000).

    CAS  Article  Google Scholar 

  21. 21

    Nieda, M. et al. Dendritic cells rapidly undergo apoptosis in vitro following culture with activated CD4+ Vα24 natural killer T cells expressing CD40L. Immunology 102, 137–145 (2001).

    CAS  Article  Google Scholar 

  22. 22

    Vieira, P.L., de Jong, E.C., Wierenga, E.A., Kapsenberg, M.L. & Kalinski, P. Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J. Immunol. 164, 4507–4512 (2000).

    CAS  Article  Google Scholar 

  23. 23

    Corinti, S., Albanesi, C., la Sala, A., Pastore, S. & Girolomoni, G. Regulatory activity of autocrine IL-10 on dendritic cell functions. J. Immunol. 166, 4312–4318 (2001).

    CAS  Article  Google Scholar 

  24. 24

    Kitamura, H. et al. The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J. Exp. Med. 189, 1121–1128 (1999).

    CAS  Article  Google Scholar 

  25. 25

    Exley, M.A. et al. Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver. J. Immunol. 168, 1519–1523 (2002).

    CAS  Article  Google Scholar 

  26. 26

    Sieling, P.A. et al. Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c. J. Immunol. 165, 5338–5344 (2000).

    CAS  Article  Google Scholar 

  27. 27

    Mailliard, R.B. et al. Complementary dendritic cell–activating function of CD8+ and CD4+ T cells: helper role of CD8+ T cells in the development of T helper type 1 responses. J. Exp. Med. 195, 473–483 (2002).

    CAS  Article  Google Scholar 

  28. 28

    Gerosa, F. et al. Reciprocal activating interaction between natural killer cells and dendritic cells. J. Exp. Med. 195, 327–333 (2002).

    CAS  Article  Google Scholar 

  29. 29

    Piccioli, D., Sbrana, S., Melandri, E. & Valiante, N.M. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J. Exp. Med. 195, 335–341 (2002).

    CAS  Article  Google Scholar 

  30. 30

    Ferlazzo, G. et al. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J. Exp. Med. 195, 343–351 (2002).

    CAS  Article  Google Scholar 

  31. 31

    Exley, M.A. et al. A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses. J. Immunol. 167, 5531–5534 (2001).

    CAS  Article  Google Scholar 

  32. 32

    Reinhardt, R.L., Khoruts, A., Merica, R., Zell, T. & Jenkins, M.K. Visualizing the generation of memory CD4 T cells in the whole body. Nature 410, 101–105 (2001).

    CAS  Article  Google Scholar 

  33. 33

    Masopust, D., Vezys, V., Marzo, A.L. & Lefrancois, L. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291, 2413–2417 (2001).

    CAS  Article  Google Scholar 

  34. 34

    Campbell, J.J. et al. Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J. Immunol. 166, 6477–6482 (2001).

    CAS  Article  Google Scholar 

  35. 35

    Kim, C.H., Johnston, B. & Butcher, E.C. Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among Vα24+Vβ11+ NKT cell subsets with distinct cytokine-producing capacity. Blood 100, 11–16 (2002).

    CAS  Article  Google Scholar 

  36. 36

    Sallusto, F. et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur. J. Immunol. 29, 1617–1625 (1999).

    CAS  Article  Google Scholar 

  37. 37

    Huang, Q. et al. The plasticity of dendritic cell responses to pathogens and their components. Science 294, 870–875 (2001).

    CAS  Article  Google Scholar 

  38. 38

    Kumar, H., Belperron, A., Barthold, S.W. & Bockenstedt, L.K. Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J. Immunol. 165, 4797–4801 (2000).

    CAS  Article  Google Scholar 

  39. 39

    Kawakami, K. et al. Monocyte chemoattractant protein-1-dependent increase of Vα14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection. J. Immunol. 167, 6525–6532 (2001).

    CAS  Article  Google Scholar 

  40. 40

    Nieuwenhuis, E.E. et al. CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nature Med. 8, 588–593 (2002).

    CAS  Article  Google Scholar 

  41. 41

    Porcelli, S. et al. Recognition of cluster of differentiation 1 antigens by human CD4CD8 cytolytic T lymphocytes. Nature 341, 447–450 (1989).

    CAS  Article  Google Scholar 

  42. 42

    Grant, E.P. et al. Molecular recognition of lipid antigens by T cell receptors. J. Exp. Med. 189, 195–205 (1999).

    CAS  Article  Google Scholar 

  43. 43

    Behar, S.M., Porcelli, S.A., Beckman, E.M. & Brenner, M.B. A pathway of costimulation that prevents anergy in CD28 T cells: B7-independent costimulation of CD1-restricted T cells. J. Exp. Med. 182, 2007–2018 (1995).

    CAS  Article  Google Scholar 

  44. 44

    Carlsson, S.R., Roth, J., Piller, F. & Fukuda, M. Isolation and characterization of human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Major sialoglycoproteins carrying polylactosaminoglycan. J. Biol. Chem. 263, 18911–18919 (1988).

    CAS  PubMed  Google Scholar 

  45. 45

    Sugita, M. et al. Separate pathways for antigen presentation by CD1 molecules. Immunity 11, 743–752 (1999).

    CAS  Article  Google Scholar 

Download references


We thank T. Yamamura for αGalCer, S.B. Wilson for helpful discussions, and M. Brigl for critical review of the manuscript. Supported by the Arthritis Foundation (M. S. V. and D. S. L.), the Arthritis National Research Foundation (M. S. V.), the Charles A. King Trust of the Medical Foundation (J. E. G.) and the NIH (grants K08AR01996 and R21AR48037 to M. S. V., K08AR02171 to D. S. L. and R37AI29873 to M. B. B.)

Author information



Corresponding author

Correspondence to Michael B. Brenner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vincent, M., Leslie, D., Gumperz, J. et al. CD1-dependent dendritic cell instruction. Nat Immunol 3, 1163–1168 (2002).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing