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TIRC7 Deficiency Causes In Vitro and In Vivo Augmentation of T and B Cell Activation and Cytokine Response

2004/08/01 by Nalân Utku, Anke Boerner, Antje Tomschegg +6 · 27 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Chemistry · Medicine · #NF-κB Signaling Pathways #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Immune Response and Inflammation #In vivo #Cytokine #In vitro #Immunology #Cell biology #Chemistry #Medicine #Biology #Biochemistry #Biotechnology

paper · pdf · doi:10.4049/jimmunol.173.4.2342

published in The Journal of Immunology 173(4), 2342-2352 (American Association of Immunologists)

openalex publication_date 2004/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11

Abstract

The membrane protein T cell immune response cDNA 7 (TIRC7) was recently identified and was shown to play an important role in T cell activation. To characterize the function of TIRC7 in more detail, we generated TIRC7-deficient mice by gene targeting. We observed disturbed T and B cell function both in vitro and in vivo in TIRC7(-/-) mice. Histologically, primary and secondary lymphoid organs showed a mixture of hypo-, hyper-, and dysplastic changes of multiple lymphohemopoietic compartments. T cells from TIRC7(-/-) mice exhibited significantly increased proliferation and expression of IL-2, IFN-gamma, and IL-4 in response to different stimuli. Resting T cells from TIRC7(-/-) mice exhibited decreased CD62L, but increased CD11a and CD44 expression, suggesting an in vivo expansion of memory/effector T cells. Remarkably, activated T cells from TIRC7(-/-) mice expressed lower levels of CTLA-4 in comparison with wild-type cells. B cells from TIRC7-deficient mice exhibited significantly higher in vitro proliferation following stimulation with anti-CD40 Ab or LPS plus IL-4. B cell hyperreactivity was reflected in vivo by elevated serum levels of various Ig classes and higher CD86 expression on B cells. Furthermore, TIRC7 deficiency resulted in an augmented delayed-type hypersensitivity response that was also reflected in increased mononuclear infiltration in the skin obtained from TIRC7-deficient mice food pads. In summary, the data strongly support an important role for TIRC7 in regulating both T and B cell responses.

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