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Laboratory of Experimental Immunology, Université Libre de Bruxelles, Brussels, Belgium
To gain insight into the defects responsible for impaired Th1
responses in human newborns, we analyzed the production of cytokines by
dendritic cells (DC) derived from cord blood monocytes. We observed
that neonatal DC generated from adherent cord blood mononuclear cells
cultured for 6 days in the presence of IL-4 and GM-CSF show a phenotype
similar to adult DC generated from adherent PBMC, although they express
lower levels of HLA-DR, CD80, and CD40. Measurement of cytokine levels
produced by neonatal DC upon stimulation by LPS, CD40 ligation, or
poly(I:C) indicated a selective defect in the synthesis of IL-12.
Determination of IL-12(p40) and IL-12(p35) mRNA levels by real-time
RT-PCR revealed that IL-12(p35) gene expression is highly
repressed in stimulated neonatal DC whereas their
IL-12(p40) gene expression is not altered. The addition of
rIFN-
to LPS-stimulated newborn DC restored their expression of
IL-12(p35) and their synthesis of IL-12 (p70) up to adult levels.
Moreover, we observed that neonatal DC are less efficient than adult DC
to induce IFN- production by allogenic adult CD4+ T
cells. This defect was corrected by the addition of rIL-12. We conclude
that neonatal DC are characterized by a severe defect in
IL-12(p35) gene expression which is responsible for an
impaired ability to elicit IFN- production by T
cells.
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F. Mascart, V. Verscheure, A. Malfroot, M. Hainaut, D. Pierard, S. Temerman, A. Peltier, A.-S. Debrie, J. Levy, G. Del Giudice, et al. Bordetella pertussis Infection in 2-Month-Old Infants Promotes Type 1 T Cell Responses J. Immunol., February 1, 2003; 170(3): 1504 - 1509. [Abstract] [Full Text] [PDF]
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J. W. Upham, P. T. Lee, B. J. Holt, T. Heaton, S. L. Prescott, M. J. Sharp, P. D. Sly, and P. G. Holt Development of Interleukin-12-Producing Capacity throughout Childhood Infect. Immun., December 1, 2002; 70(12): 6583 - 6588. [Abstract] [Full Text] [PDF]
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H. Karlsson, C. Hessle, and A. Rudin Innate Immune Responses of Human Neonatal Cells to Bacteria from the Normal Gastrointestinal Flora Infect. Immun., December 1, 2002; 70(12): 6688 - 6696. [Abstract] [Full Text] [PDF]
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P.G. Holt and P. D. Sly Interactions between RSV Infection, Asthma, and Atopy: Unraveling the Complexities J. Exp. Med., November 18, 2002; 196(10): 1271 - 1275. [Full Text] [PDF]
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B. Adkins, Y. Bu, and P. Guevara Murine Neonatal CD4+ Lymph Node Cells Are Highly Deficient in the Development of Antigen-Specific Th1 Function in Adoptive Adult Hosts J. Immunol., November 1, 2002; 169(9): 4998 - 5004. [Abstract] [Full Text] [PDF]
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M. Wysocka, M. H. Zaki, L. E. French, J. Chehimi, M. Shapiro, S. E. Everetts, K. S. McGinnis, L. Montaner, and A. H. Rook Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines Blood, October 16, 2002; 100(9): 3287 - 3294. [Abstract] [Full Text] [PDF]
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M. A. McDowell, M. Marovich, R. Lira, M. Braun, and D. Sacks Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent Infect. Immun., August 1, 2002; 70(8): 3994 - 4001. [Abstract] [Full Text] [PDF]
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H. Jakobsen, S. Bjarnarson, G. Del Giudice, M. Moreau, C.-A. Siegrist, and I. Jonsdottir Intranasal Immunization with Pneumococcal Conjugate Vaccines with LT-K63, a Nontoxic Mutant of Heat-Labile Enterotoxin, as Adjuvant Rapidly Induces Protective Immunity against Lethal Pneumococcal Infections in Neonatal Mice Infect. Immun., March 1, 2002; 70(3): 1443 - 1452. [Abstract] [Full Text] [PDF]
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H. H. Smits, E. C. de Jong, J. H. N. Schuitemaker, T. B. H. Geijtenbeek, Y. van Kooyk, M. L. Kapsenberg, and E. A. Wierenga Intercellular Adhesion Molecule-1/LFA-1 Ligation Favors Human Th1 Development J. Immunol., February 15, 2002; 168(4): 1710 - 1716. [Abstract] [Full Text] [PDF]
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M. O. C. Ota, J. Vekemans, S. E. Schlegel-Haueter, K. Fielding, M. Sanneh, M. Kidd, M. J. Newport, P. Aaby, H. Whittle, P.-H. Lambert, et al. Influence of Mycobacteriumbovis Bacillus Calmette-Guerin on Antibody and Cytokine Responses to Human Neonatal Vaccination J. Immunol., January 15, 2002; 168(2): 919 - 925. [Abstract] [Full Text] [PDF]
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