TRANCE-RANK Costimulation is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania major Infection in CD40L-Deficient Mice

Padigel, Udaikumar M; Kim, Nacksung; Choi, Yongwon; Farrell, Jay P

doi:10.4049/jimmunol.171.10.5437

Cited by 36Research on Leishmaniasis StudiesT-cell and B-cell ImmunologyImmune Response and Inflammation

TRANCE-RANK Costimulation is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania major Infection in CD40L-Deficient Mice

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Padigel, Udaikumar M, Kim, Nacksung, Choi, Yongwon, Farrell, Jay P·2003·The Journal of Immunology

DOI 10.4049/jimmunol.171.10.5437

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Abstract

Blockade of TNF-related activation-induced cytokine (TRANCE)-receptor activator of NF-κB (RANK) interaction reverses healing in CD40L−/− mice infected with Leishmania major. Although previous studies demonstrated a requirement for CD40-CD40L interaction in production of IL-12 and the development of resistance to Leishmania infection, we recently showed that CD40L−/− mice control infection when inoculated with low numbers of parasites and that cells from these mice produce IL-12. Here, we show that in vivo treatment with a TRANCE receptor fusion protein results in a decrease in numbers of IL-12 producing cells as well as a shift from a dominant Th1 to Th2 type response in infected mice. These results demonstrate that CD40L−/− mice use the TRANCE-RANK costimulatory pathway to promote IL-12 production and the activation of a protective Th1 type response.

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The CD40L-CD40 pathway is apparently able to compensate for total absence of RANK-RANKL signaling in knockout mouse studies.
“This important pathway is apparently able to compensate for the total absence of RANK-RANKL signaling in knockout mouse studies (171,172).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [172]
RANKL inhibition has no significant effects on in vivo responses to immune challenges in genetically intact animals.
“Several studies have shown that RANKL inhibition had no significant effects on the in vivo responses to immune challenges in genetically intact animals (171-174).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [172]

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Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308 · see citing works
Development of T H 1 CD4 + T Cells Through IL-12 Produced by Listeria -Induced Macrophages
Hsieh, C.-S., Macatonia, S. E., Tripp, C. S., Wolf, S. F., O'Garra, A., & Murphy, K. M. (1993) · Science · doi:10.1126/science.8097338 · Cited by 3,134 · see citing works
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290 · see citing works
Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L., & Locksley, R. M. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.1.59 · Cited by 1,454 · see citing works
TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor.
Wong, B. R., Josien, R., Lee, S. Y., Sauter, B., Li, H.-L., Steinman, R. M., & Choi, Y. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.12.2075 · Cited by 853 · see citing works
Self-citation
RANK-L and RANK: T Cells, Bone Loss, and Mammalian Evolution
Theill, L. E., Boyle, W. J., & Penninger, J. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064753 · Cited by 817 · see citing works
Recombinant interleukin 12 cures mice infected with Leishmania major.
Heinzel, F. P., Schoenhaut, D. S., Rerko, R. M., Rosser, L. E., & Gately, M. K. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.5.1505 · Cited by 761 · see citing works
Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.
Sypek, J. P., Chung, C. L., Mayor, S. E., Subramanyam, J. M., Goldman, S. J., Sieburth, D., Wolf, S. F., & Schaub, R. G. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1797 · Cited by 721 · see citing works
The Adjuvant Effect of Interleukin-12 in a Vaccine Against Leishmania major
Afonso, L., Scharton, T. M., Vieira, L. Q., Wysocka, M., Trinchieri, G., & Scott, P. (1994) · Science · doi:10.1126/science.7904381 · Cited by 680 · see citing works
Identification of an Infective Stage of Leishmania Promastigotes
Sacks, D. L., & Perkins, P. V. (1984) · Science · doi:10.1126/science.6701528 · Cited by 498 · see citing works
Genetically resistant mice lacking interleukin‐12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response
Mattner, F., Magram, J., Ferrante, J., Launois, P., Padova, K. D., Behin, R., Gately, M. K., Louis, J. A., & Alber, G. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260722 · Cited by 469 · see citing works
IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis.
Scharton‐Kersten, T., Afonso, L., Wysocka, M., Trinchieri, G., & Scott, P. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.10.5320 · Cited by 414 · see citing works
Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection.
Reiner, S. L., Zheng, S., Wang, Z., Stowring, L., & Locksley, R. M. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.447 · Cited by 363 · see citing works
CD40 Ligand Is Required for Protective Cell-Mediated Immunity to Leishmania major
Campbell, K. A., Ovendale, P. J., Kennedy, M. K., Fanslow, W. C., Reed, S. G., & Maliszewski, C. R. (1996) · Immunity · doi:10.1016/s1074-7613(00)80436-7 · Cited by 321 · see citing works
TRANCE, a TNF Family Member, Is Differentially Expressed on T Cell Subsets and Induces Cytokine Production in Dendritic Cells
Josien, R., Wong, B. R., Li, H., Steinman, R. M., & Choi, Y. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.5.2562 · Cited by 317 · see citing works
Self-citation
Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice.
Carrera, L., Gazzinelli, R. T., Badolato, R., Hieny, S. E., Müller, W., Kühn, R., & Sacks, D. L. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.2.515 · Cited by 312 · see citing works
Disruption of CD40–CD40 Ligand Interactions Results in an Enhanced Susceptibility to Leishmania amazonensis Infection
Soong, L., Xu, J., Grewal, I. S., et al. (1996) · Immunity · doi:10.1016/s1074-7613(00)80434-3 · Cited by 306 · see citing works
Protective Role of CD40 in Leishmania major Infection at Two Distinct Phases of Cell-Mediated Immunity
Kamanaka, M., Yu, P., Yasui, T., Yoshida, K., Kawabe, T., Horii, T., Kishimoto, T., & Kikutani, H. (1996) · Immunity · doi:10.1016/s1074-7613(00)80435-5 · Cited by 294 · see citing works
Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection.
Morris, S. C., Madden, K. B., Adamovicz, J. J., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.3.1047 · Cited by 286 · see citing works
Uptake of Leishmania major Amastigotes Results in Activation and Interleukin 12 Release from Murine Skin–derived Dendritic Cells: Implications for the Initiation of Anti-Leishmania Immunity
von Stebut, E., Belkaid, Y., Jakob, T., et al. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.8.1547 · Cited by 285 · see citing works
TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation.
Bachmann, M. F., Wong, B. R., Josien, R., Steinman, R. M., Oxenius, A., & Choi, Y. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.7.1025 · Cited by 260 · see citing works
Self-citation
Murine cutaneous leishmaniasis : Susceptibility correlates with differential expansion of helper T-cell subsets
Locksley, R. M., Heinzel, F. P., Sadick, M. D., et al. (1987) · Annales de l Institut Pasteur Immunologie · doi:10.1016/s0769-2625(87)80030-2 · Cited by 215 · see citing works
IL-12 Is Required to Maintain a Th1 Response During Leishmania major Infection
Park, A. Y., Hondowicz, B. D., & Scott, P. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.2.896 · Cited by 204 · see citing works
The role of antigen and IL-12 in sustaining Th1 memory cells in vivo : IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge
Stobie, L., Gurunathan, S., Prussin, C., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160197797 · Cited by 196 · see citing works
Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice
Heinzel, F. P., Rerko, R. M., Ahmed, F., et al. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.2.730 · Cited by 162 · see citing works
LeIF: A Recombinant Leishmania Protein That Induces an IL-12-Mediated Th1 Cytokine Profile
Skeiky, Y. A. W., Kennedy, M. K., Kaufman, D., et al. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.11.6171 · Cited by 146 · see citing works
Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy
Ball, T., Sperr, W. R., Valent, P., Lidholm, J., Spitzauer, S., Ebner, C., Kraft, D., & Valenta, R. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199906)29:06 · Cited by 141 · see citing works
IL-12p70 Production by Leishmania major -Harboring Human Dendritic Cells Is a CD40/CD40 Ligand-Dependent Process
Marovich, M., McDowell, M. A., Thomas, E. K., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5858 · Cited by 124 · see citing works
LeishmaniaPriming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent
McDowell, M. A., Marovich, M., Lira, R., et al. (2002) · Infection and Immunity · doi:10.1128/iai.70.8.3994-4001.2002 · Cited by 95 · see citing works
The Role of IL-12 in Maintaining Resistance to Leishmania major
Park, A. Y., Hondowicz, B. D., Köpf, M., & Scott, P. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5771 · Cited by 87 · see citing works
Interferon-γ Directly Inhibits TRANCE-Induced Osteoclastogenesis
Fox, S. W., & Chambers, T. J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3577 · Cited by 82 · see citing works
Constitutive expression of Bcl-xL or Bcl-2 prevents peptide antigen-induced T cell deletion but does not influence T cell homeostasis after a viral infection
Petschner, F., Zimmermann, C., Strasser, A., Grillot, D., Núñez, G., & Pircher, H. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199802)28:02 · Cited by 77 · see citing works
Preformed Membrane-Associated Stores of Interleukin (Il)-12 Are a Previously Unrecognized Source of Bioactive IL-12 That Is Mobilized within Minutes of Contact with an Intracellular Parasite
Quinones, M. P., Ahuja, S. K., Melby, P. C., Pate, L., Reddick, R. L., & Ahuja, S. S. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.507 · Cited by 70 · see citing works
Underproduction of Interleukin-12 in Susceptible Mice during Progressive Leishmaniasis Is Due to Decreased CD40 Activity
Heinzel, F. P., Rerko, R. M., & Hujer, A. M. (1998) · Cellular Immunology · doi:10.1006/cimm.1998.1267 · Cited by 55 · see citing works
Depletion of interleukin-4 in BALB/c mice with established Leishmania major infections increases the efficacy of antimony therapy and promotes Th1-like responses
Nabors, G. S., & Farrell, J. P. (1994) · Infection and Immunity · doi:10.1128/iai.62.12.5498-5504.1994 · Cited by 40 · see citing works
Self-citation
Suppression of IL-12 Production by Soluble CD40 Ligand: Evidence for Involvement of the p44/42 Mitogen-Activated Protein Kinase Pathway
Wittmann, M., Kienlin, P., Mommert, S., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.8.3793 · Cited by 35 · see citing works
The Development of a Th1-Type Response and Resistance to Leishmania major Infection in the Absence of CD40-CD40L Costimulation
Padigel, U. M., Perrin, P. J., & Farrell, J. P. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5874 · Cited by 27 · see citing works
Self-citation
In vivo alterations in cytokine production following interleukin-12 (IL-12) and anti-IL-4 antibody treatment of CB6F1 mice with chronic cutaneous leishmaniasis
Li, J., Scott, P., & Farrell, J. P. (1996) · Infection and Immunity · doi:10.1128/iai.64.12.5248-5254.1996 · Cited by 19 · see citing works
Self-citation
CD4+ T cell subsets in experimental cutaneous leishmaniasis
Scott, P., Natovitz, P., Coffman, R. L., et al. (1988) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02761988000500006 · Cited by 18 · see citing works
CD40-CD40 Ligand Costimulation Is Not Required for Initiation and Maintenance of a Th1-Type Response to Leishmania major Infection
Padigel, U. M., & Farrell, J. P. (2003) · Infection and Immunity · doi:10.1128/iai.71.3.1389-1395.2003 · Cited by 18 · see citing works
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Stolina, M., Dwyer, D., Ominsky, M. S., Corbin, T., Van, G., Bolon, B., Sarosi, I., McCabe, J., Zack, D. J., & Kostenuik, P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7497 · Cited by 63 · see citing works

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Authors: Padigel, U. M., Kim, N., Choi, Y., & Farrell, J. P.
Affiliations: University of Pennsylvania (US)
ORCID: Padigel, Udaikumar M
Kim, Nacksung
Choi, Yongwon
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2003-11
Volume: 171
Issue: 10
Pages: 5437-5441
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.171.10.5437
OpenAlex: W2107506804
Cited by: 36
References: 40
Citations by year: 2026: 2 · 2025: 3 · 2021: 3 · 2020: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2012: 2
FWCI: 1.69
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ai027828-09)
National Institute of Allergy and Infectious Diseases (AI-27828)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: CD40 ligand, IL-12 production, Th1 response, Th2 immune response, CD40-CD40L interaction, cutaneous leishmaniasis, costimulatory pathways
MeSH terms: Animals, Carrier Proteins, Cells, Cultured, Female, Glycoproteins, Humans, Immunoglobulin Fc Fragments, Lymph Nodes, Membrane Glycoproteins, Mice, Inbred C57BL, Recombinant Fusion Proteins, Signal Transduction, Down-Regulation, Immunophenotyping, Leishmaniasis, Cutaneous, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Leishmania major, Mice, Knockout, Th1 Cells, Interleukin-12, CD40 Ligand, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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TRANCE-RANK Costimulation is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania major Infection in CD40L-Deficient Mice

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