Generation and characterization of B7-H4/B7S1/B7x-deficient mice |
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| Authors: | 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 |
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| Affiliation: | Campbell Family Institute for Breast Cancer Research, 620 University Ave., Suite 706, Toronto, Ontario, Canada. woong-kyung.suh@ircm.qc.ca |
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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. |
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