International Immunology, Vol. 5, No. 9, pp. 1119-1128,September 1993
© 1993 Japanese Society for Immunology
Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from 
ß TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-
production is IFN--dependent
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology 901 California Avenue, Palo Alto, CA 94304, USA
1 Department of Pathology, Washington University School of Medicine St Louis, MO 63110, USA
Correspondence to: Correspondence to: A. O'Gara
We have examined the antigen presenting cell (APC) requirements for primary T cell activation and T helper (Th) cell phenotype differentiation using naive CD4+ T cells from 
ß TCR transgenic mice. Purified dendritic cells were the principal cell required for induction of primary ovalbumln peptide specific T cell activation and clonal expansion. However, dendritic cells did not induce differentiation of T cells toward Th1 or Th2 phenotype. Addition of IL-4 during primary dendritic cell stimulations of T cells resulted in the development of a Th2 phenotype which produced high levels of IL-4 during secondary and tertiary stimulation. In contrast, development of Th1 cells producing high levels of IFN-
could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages. Addition of splenic or peritoneal B cells did not induce Th1 development. Activated splenic macrophages induced Th1 development via a non-MHC restricted mechanism. Thus, requirements for induction of proliferation of naive CD4+ T cells are distinct from those directing Th1 phenotype development. IL-12 could replace the requirement for macrophages to induce Th1 development when T cells were activated with dendritic cells. Furthermore, this IL-12 mediated development of Th1 cells producing high levels of IFN- was dependent on IFN-.
Keywords: dendritic cells, IFN-, IL-12, macrophages, TCR transgenic T cells
Received 23 March 1993, accepted 2 June 1993.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Sharma and R. Madhubala Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains of Leishmania donovani J. Immunol., December 15, 2009; 183(12): 7719 - 7731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Y. Wan and R. A. Flavell How Diverse--CD4 Effector T Cells and their Functions J Mol Cell Biol, October 1, 2009; 1(1): 20 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sasaki, N. Suzuki, R. Kent Jr., N. Kawashima, J. Takeda, and P. Stashenko T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice J. Immunol., May 1, 2008; 180(9): 6193 - 6198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mott, D. J. Brick, N. van Rooijen, and H. Ghiasi Macrophages Are Important Determinants of Acute Ocular HSV-1 Infection in Immunized Mice Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5605 - 5615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sel, M. Wegmann, S. Sel, S. Bauer, H. Garn, G. Alber, and H. Renz Immunomodulatory Effects of Viral TLR Ligands on Experimental Asthma Depend on the Additive Effects of IL-12 and IL-10 J. Immunol., June 15, 2007; 178(12): 7805 - 7813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mejri and M. Brossard Splenic dendritic cells pulsed with Ixodes ricinus tick saliva prime naive CD4+T to induce Th2 cell differentiation in vitro and in vivo Int. Immunol., April 1, 2007; 19(4): 535 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schott Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocr. Relat. Cancer, September 1, 2006; 13(3): 779 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Berberich-Siebelt, I. Berberich, M. Andrulis, B. Santner-Nanan, M. K. Jha, S. Klein-Hessling, A. Schimpl, and E. Serfling SUMOylation Interferes with CCAAT/Enhancer-Binding Protein beta-Mediated c-myc Repression, but Not IL-4 Activation in T Cells. J. Immunol., April 15, 2006; 176(8): 4843 - 4851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mikhalkevich, B. Becknell, M. A. Caligiuri, M. D. Bates, R. Harvey, and W.-p. Zheng Responsiveness of Naive CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation J. Immunol., February 1, 2006; 176(3): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kimura, S.-C. Tzou, R. Rocchi, M. Kimura, K. Suzuki, A. F. Parlow, N. R. Rose, and P. Caturegli Interleukin (IL)-12-Driven Primary Hypothyroidism: the Contrasting Roles of Two Th1 Cytokines (IL-12 and Interferon-{gamma}) Endocrinology, August 1, 2005; 146(8): 3642 - 3651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-J. Ruth, A. R. Kitching, M. Li, T. J. Semple, J. R. Timoshanko, P. G. Tipping, and S. R. Holdsworth An IL-12-Independent Role for CD40-CD154 in Mediating Effector Responses: Studies in Cell-Mediated Glomerulonephritis and Dermal Delayed-Type Hypersensitivity J. Immunol., July 1, 2004; 173(1): 136 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bitsaktsis, J. Huntington, and G. Winslow Production of IFN-{gamma} by CD4 T Cells Is Essential for Resolving Ehrlichia Infection J. Immunol., June 1, 2004; 172(11): 6894 - 6901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Koski, K. Kariko, S. Xu, D. Weissman, P. A. Cohen, and B. J. Czerniecki Cutting Edge: Innate Immune System Discriminates between RNA Containing Bacterial versus Eukaryotic Structural Features That Prime for High-Level IL-12 Secretion by Dendritic Cells J. Immunol., April 1, 2004; 172(7): 3989 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Laine, M.-C. Trescol-Biemont, S. Longhi, G. Libeau, J. C. Marie, P.-O. Vidalain, O. Azocar, A. Diallo, B. Canard, C. Rabourdin-Combe, et al. Measles Virus (MV) Nucleoprotein Binds to a Novel Cell Surface Receptor Distinct from Fc{gamma}RII via Its C-Terminal Domain: Role in MV-Induced Immunosuppression J. Virol., November 1, 2003; 77(21): 11332 - 11346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Brown, E. L. Lee, and D. L. Thiele TNF Enhances CD4+ T Cell Alloproliferation, IFN-{gamma} Responses, and Intestinal Graft-Versus-Host Disease by IL-12-Independent Mechanisms J. Immunol., May 15, 2003; 170(10): 5082 - 5088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aseffa, A. Gumy, P. Launois, H. R. MacDonald, J. A. Louis, and F. Tacchini-Cottier The Early IL-4 Response to Leishmania major and the Resulting Th2 Cell Maturation Steering Progressive Disease in BALB/c Mice Are Subject to the Control of Regulatory CD4+CD25+ T Cells J. Immunol., September 15, 2002; 169(6): 3232 - 3241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Peterson, I. Stromnes, R. Messer, K. Hasenkrug, and B. Chesebro Novel Role of CD8+ T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4+ Th1 Responses during Retrovirus Infection in Mice J. Virol., July 17, 2002; 76(16): 7942 - 7948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nguyen, W. R. Burack, J. L. Stock, R. Kortum, O. V. Chaika, M. Afkarian, W. J. Muller, K. M. Murphy, D. K. Morrison, R. E. Lewis, et al. Kinase Suppressor of Ras (KSR) Is a Scaffold Which Facilitates Mitogen-Activated Protein Kinase Activation In Vivo Mol. Cell. Biol., May 1, 2002; 22(9): 3035 - 3045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Lindsay, C. J. Ciesielski, T. Scheinin, H. J. Hodgson, and F. M. Brennan The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10 J. Immunol., June 15, 2001; 166(12): 7625 - 7633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Horwood, J. Elliott, T. J. Martin, and M. T. Gillespie IL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro J. Immunol., April 15, 2001; 166(8): 4915 - 4921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Haupt, F. Siegel, M. Lu, D. Yang, G. Hilken, K. Mann, M. Roggendorf, and B. Saller Induction of a Cellular and Humoral Immune Response against Preprocalcitonin by Genetic Immunization: A Potential New Treatment for Medullary Thyroid Carcinoma Endocrinology, March 1, 2001; 142(3): 1017 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-F. Yang, M. Tomura, S. Ono, T. Hamaoka, and H. Fujiwara Requirement for IFN-{gamma} in IL-12 production induced by collaboration between V{alpha}14+ NKT cells and antigen-presenting cells Int. Immunol., December 1, 2000; 12(12): 1669 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Glimcher and K. M. Murphy Lineage commitment in the immune system: the T helper lymphocyte grows up Genes & Dev., July 15, 2000; 14(14): 1693 - 1711. [Full Text]
|
|
|
|
|
|
P. L. Vieira, E. C. de Jong, E. A. Wierenga, M. L. Kapsenberg, and P. Kalinski Development of Th1-Inducing Capacity in Myeloid Dendritic Cells Requires Environmental Instruction J. Immunol., May 1, 2000; 164(9): 4507 - 4512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Jankovic, M. C. Kullberg, N. Noben-Trauth, P. Caspar, W. E. Paul, and A. Sher Single Cell Analysis Reveals That IL-4 Receptor/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+ Lymphocytes with a Th2 Cytokine Profile J. Immunol., March 15, 2000; 164(6): 3047 - 3055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vukmanovic-Stejic, B. Vyas, P. Gorak-Stolinska, A. Noble, and D. M. Kemeny Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes Blood, January 1, 2000; 95(1): 231 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. v. Wely, P. C. L. Beverley, S. J. Brett, C. J. Britten, and J. P. Tite Expression of L-Selectin on Th1 Cells Is Regulated by IL-12 J. Immunol., August 1, 1999; 163(3): 1214 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mukhopadhyay, P. K. Sahoo, A. George, V. Bal, S. Rath, and B. Ravindran Delayed Clearance of Filarial Infection and Enhanced Th1 Immunity Due to Modulation of Macrophage APC Functions in xid Mice J. Immunol., July 15, 1999; 163(2): 875 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sugie, T. Tomura, K. Takakura, T. Kawano, M. Taniguchi, H. M. Grey, and K. Ishizaka Target cells for an immunosuppressive cytokine, glycosylation-inhibiting factor Int. Immunol., July 1, 1999; 11(7): 1149 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tomura, W.-G. Yu, H.-J. Ahn, M. Yamashita, Y.-F. Yang, S. Ono, T. Hamaoka, T. Kawano, M. Taniguchi, Y. Koezuka, et al. A Novel Function of V{alpha}14+CD4+NKT Cells: Stimulation of IL-12 Production by Antigen-Presenting Cells in the Innate Immune System J. Immunol., July 1, 1999; 163(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Garcia, K. Uyemura, P. A. Sieling, M. T. Ochoa, C. T. Morita, H. Okamura, M. Kurimoto, T. H. Rea, and R. L. Modlin IL-18 Promotes Type 1 Cytokine Production from NK Cells and T Cells in Human Intracellular Infection J. Immunol., May 15, 1999; 162(10): 6114 - 6121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tanabe, H. Xiong, T. Nomura, M. Arakawa, and M. Mitsuyama Induction of Protective T Cells against Listeria monocytogenes in Mice by Immunization with a Listeriolysin O-Negative Avirulent Strain of Bacteria and Liposome-Encapsulated Listeriolysin O Infect. Immun., February 1, 1999; 67(2): 568 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Alexander, A. Satoskar, and D. Russell Leishmania species: models of intracellular parasitism J. Cell Sci., January 9, 1999; 112(18): 2993 - 3002. [Abstract] [PDF]
|
|
|
|
 |
|
 P. A. Stumbles, J. A. Thomas, C. L. Pimm, P. T. Lee, T. J. Venaille, S. Proksch, and P. G. Holt Resting Respiratory Tract Dendritic Cells Preferentially Stimulate T Helper Cell Type 2 (Th2) Responses and Require Obligatory Cytokine Signals for Induction of Th1 Immunity J. Exp. Med., December 7, 1998; 188(11): 2019 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Himmelrich, C. Parra-Lopez, F. Tacchini-Cottier, J. A. Louis, and P. Launois The IL-4 Rapidly Produced in BALB/c Mice After Infection with Leishmania major Down-Regulates IL-12 Receptor {beta}2-Chain Expression on CD4+ T Cells Resulting in a State of Unresponsiveness to IL-12 J. Immunol., December 1, 1998; 161(11): 6156 - 6163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Wakil, Z.-E. Wang, J. C. Ryan, D. J. Fowell, and R. M. Locksley Interferon {gamma} Derived from CD4+ T Cells Is Sufficient to Mediate T Helper Cell Type 1 Development J. Exp. Med., November 2, 1998; 188(9): 1651 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brewer, L. Tetley, J. Richmond, F. Y. Liew, and J. Alexander Lipid Vesicle Size Determines the Th1 or Th2 Response to Entrapped Antigen J. Immunol., October 15, 1998; 161(8): 4000 - 4007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Maekawa, K. Himeno, H. Ishikawa, H. Hisaeda, T. Sakai, T. Dainichi, T. Asao, R. A Good, and N. Katunuma Switch of CD4+ T Cell Differentiation from Th2 to Th1 by Treatment with Cathepsin B Inhibitor in Experimental Leishmaniasis J. Immunol., September 1, 1998; 161(5): 2120 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Ahuja, S. Mummidi, H. L. Malech, and S. K. Ahuja Human Dendritic Cell (DC)-Based Anti-Infective Therapy: Engineering DCs to Secrete Functional IFN-{gamma} and IL-12 J. Immunol., July 15, 1998; 161(2): 868 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Singh, S. Bhatia, R. Abraham, S. K. Basu, A. George, V. Bal, and S. Rath Modulation of T Cell Cytokine Profiles and Peptide-MHC Complex Availability In Vivo by Delivery to Scavenger Receptors via Antigen Maleylation J. Immunol., May 15, 1998; 160(10): 4869 - 4880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Dey, Y.-G. Yang, G. L. Szot, D. A. Pearson, and M. Sykes Interleukin-12 Inhibits Graft-Versus-Host Disease Through an Fas-Mediated Mechanism Associated With Alterations in Donor T-Cell Activation and Expansion Blood, May 1, 1998; 91(9): 3315 - 3322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Peterson, L. A. Herzenberg, K. Vasquez, and C. Waltenbaugh Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns PNAS, March 17, 1998; 95(6): 3071 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Langhorne, C. Cross, E. Seixas, C. Li, and T. von der Weid A role for B cells in the development of T cell helper function in a malaria infection in mice PNAS, February 17, 1998; 95(4): 1730 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shibuya, D. Robinson, F. Zonin, S. B. Hartley, S. E. Macatonia, C. Somoza, C. A. Hunter, K. M. Murphy, and A. O'Garra IL-1{alpha} and TNF-{alpha} Are Required for IL-12-Induced Development of Th1 Cells Producing High Levels of IFN-{gamma} in BALB/c But Not C57BL/6 Mice J. Immunol., February 15, 1998; 160(4): 1708 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Chow, B.-L. Chiang, Y.-L. Lee, W.-K. Chi, W.-C. Lin, Y.-T. Chen, and M.-H. Tao Development of Th1 and Th2 Populations and the Nature of Immune Responses to Hepatitis B Virus DNA Vaccines Can Be Modulated by Codelivery of Various Cytokine Genes J. Immunol., February 1, 1998; 160(3): 1320 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pasare, V. Morafo, M. Entringer, P. Bansal, A. George, V. Bal, S. Rath, and J. M. Durdik Presence of Activated Antigen-Binding B Cells During Immunization Enhances Relative Levels of IFN-{gamma} in T Cell Responses J. Immunol., January 15, 1998; 160(2): 778 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. e Sousa, S. Hieny, T. Scharton-Kersten, D. Jankovic, H. Charest, R. N. Germain, and A. Sher In Vivo Microbial Stimulation Induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas J. Exp. Med., December 1, 1997; 186(11): 1819 - 1829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Szabo, A. S. Dighe, U. Gubler, and K. M. Murphy Regulation of the Interleukin (IL)-12R {beta}2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells J. Exp. Med., March 3, 1997; 185(5): 817 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Afonso, T. Scharton, L. Vieira, M Wysocka, G Trinchieri, and P Scott The adjuvant effect of interleukin-12 in a vaccine against Leishmania major Science, January 14, 1994; 263(5144): 235 - 237. [Abstract] [PDF]
|
|
|
|
|
|
M Clerici, D. Lucey, J. Berzofsky, L. Pinto, T. Wynn, S. Blatt, M. Dolan, C. Hendrix, S. Wolf, and G. Shearer Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro Science, December 10, 1993; 262(5140): 1721 - 1724. [Abstract] [PDF]
|
|