Generation and characterization of B7-H4/B7S1/B7x-deficient mice

Woong Kyung Suh, Seng Wang, Gordon S. Duncan, Yoshiyuki Miyazaki, Elizabeth Cates, Tina Walker, Beata U. Gajewska, Elissa Deenick, Wojciech Dawicki, Hitoshi Okada, Andrew Wakeham, Annick Itie, Tania H. Watts, Pamela S. Ohashi, Manel Jordana, Hiroki Yoshida, Tak W. Mak

Research output: Contribution to journalArticle

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Abstract

Members of the B7 family of cosignaling molecules regulate T-cell proliferation and effector functions by engaging cognate receptors on T cells. In vitro and in vivo blockade experiments indicated that B7-H4 (also known as B7S1 or B7x) inhibits proliferation, cytokine production, and cytotoxicity of T cells. B7-H4 binds to an unknown receptor(s) that is expressed on activated T cells. However, whether B7-H4 plays nonredundant immune regulatory roles in vivo has not been tested. We generated B7-H4-deficient mice to investigate the roles of B7-H4 during various immune reactions. Consistent with its inhibitory function in vitro, B7-H4-deficient mice mounted mildly augmented T-helper 1 (Th1) responses and displayed slightly lowered parasite burdens upon Leishmania major infection compared to the wild-type mice. However, the lack of B7-H4 did not affect hypersensitive inflammatory responses in the airway or skin that are induced by either Th1 or Th2 cells. Likewise, B7-H4-deficient mice developed normal cytotoxic T-lymphocyte reactions against viral infection. Thus, B7-H4 plays a negative regulatory role in vivo but the impact of B7-H4 deficiency is minimal. These results suggest that B7-H4 is one of multiple negative cosignaling molecules that collectively provide a fine-tuning mechanism for T-cell-mediated immune responses.

Original languageEnglish
Pages (from-to)6403-6411
Number of pages9
JournalMolecular and Cellular Biology
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 1 2006
Externally publishedYes

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T-Lymphocytes
Leishmania major
Th2 Cells
Th1 Cells
Cytotoxic T-Lymphocytes
Virus Diseases
T-Cell Antigen Receptor
Parasites
Cell Proliferation
Cytokines
Skin
Infection
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Suh, W. K., Wang, S., Duncan, G. S., Miyazaki, Y., Cates, E., Walker, T., ... Mak, T. W. (2006). Generation and characterization of B7-H4/B7S1/B7x-deficient mice. Molecular and Cellular Biology, 26(17), 6403-6411. https://doi.org/10.1128/MCB.00755-06

Generation and characterization of B7-H4/B7S1/B7x-deficient mice. / Suh, Woong Kyung; Wang, Seng; Duncan, Gordon S.; Miyazaki, Yoshiyuki; Cates, Elizabeth; Walker, Tina; Gajewska, Beata U.; Deenick, Elissa; Dawicki, Wojciech; Okada, Hitoshi; Wakeham, Andrew; Itie, Annick; Watts, Tania H.; Ohashi, Pamela S.; Jordana, Manel; Yoshida, Hiroki; Mak, Tak W.

In: Molecular and Cellular Biology, Vol. 26, No. 17, 01.09.2006, p. 6403-6411.

Research output: Contribution to journalArticle

Suh, WK, Wang, S, Duncan, GS, Miyazaki, Y, Cates, E, Walker, T, Gajewska, BU, Deenick, E, Dawicki, W, Okada, H, Wakeham, A, Itie, A, Watts, TH, Ohashi, PS, Jordana, M, Yoshida, H & Mak, TW 2006, 'Generation and characterization of B7-H4/B7S1/B7x-deficient mice', Molecular and Cellular Biology, vol. 26, no. 17, pp. 6403-6411. https://doi.org/10.1128/MCB.00755-06
Suh, Woong Kyung ; Wang, Seng ; Duncan, Gordon S. ; Miyazaki, Yoshiyuki ; Cates, Elizabeth ; Walker, Tina ; Gajewska, Beata U. ; Deenick, Elissa ; Dawicki, Wojciech ; Okada, Hitoshi ; Wakeham, Andrew ; Itie, Annick ; Watts, Tania H. ; Ohashi, Pamela S. ; Jordana, Manel ; Yoshida, Hiroki ; Mak, Tak W. / Generation and characterization of B7-H4/B7S1/B7x-deficient mice. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 17. pp. 6403-6411.
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