TIRC7 deficiency causes in vitro and in vivo augmentation of T and B cell activation and cytokine response.
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.
Utku
Nalân
N
Institut für Medizinische Immunologie, Charité-Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany. nalan.utku@charite.de
Boerner
Anke
A
Tomschegg
Antje
A
Bennai-Sanfourche
Fatima
F
Bulwin
Grit-Carsta
GC
Heinemann
Thomas
T
Loehler
Jürgen
J
Blumberg
Richard S
RS
Volk
Hans-Dieter
HD
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005434:Flow Cytometry; D018390:Gene Targeting; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D021122:Protein Subunits / Q000172:deficiency / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D025262:Vacuolar Proton-Translocating ATPases / Q000172:deficiency / Q000276:immunology*
D016207:Cytokines; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases