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Semaphorin 7A protein variants differentially regulate T‐cell activity
Author(s) -
Gras Christiane,
EizVesper Britta,
Seltsam Axel,
Immenschuh Stephan,
Blasczyk Rainer,
Figueiredo Constança
Publication year - 2013
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2012.03812.x
Subject(s) - granzyme b , biology , t cell , microbiology and biotechnology , antigen , granzyme , cytotoxic t cell , immunology , immune system , cd8 , perforin , genetics , in vitro
BACKGROUND: Semaphorin 7A (Sema7A) carries the John‐Milton‐Hagen human blood group antigen on red blood cells and shows molecular diversity. It is known that Sema7A has immunomodulatory functions, but its regulatory effects on T‐cell activation are not completely understood. In this study, the functional role of the R461C Sema7A polymorphism on T‐cell responses was investigated. STUDY DESIGN AND METHODS: Soluble recombinant wild‐type Sema7A (Sema7A_wt) and its R461C variant (Sema7A_R461C) were produced in human embryonic kidney cells. Specific assays were performed to determine the effects of Sema7A_wt and Sema7A_R461C on T‐cell activation in terms of proliferation, phenotypic alterations, granzyme B transcript levels, and secretion of proinflammatory cytokines. RESULTS: Sema7A_wt did not affect T‐cell activity, but Sema7A_R461C led to marked antigen‐independent activation of T cells. In the presence of antigen stimulation, Sema7A_R461C had a major costimulatory effect on T‐cell response. Upon Sema7A_R461C stimulation, CD4+ T cells strongly proliferated and exhibited a cytotoxic phenotype with significant up regulation of granzyme B transcripts (up to 220‐fold), even in the absence of antigen stimulation. Antibody blocking studies indicated that Sema7A_R461C‐mediated T‐cell activation is largely β1 integrin dependent. CONCLUSION: These data demonstrate that Sema7A_R461C, unlike wild‐type Sema7A, causes differential regulation of T‐cell responses. Since Sema7A has important immunomodulatory functions in inflammatory responses, it might play a key role in autoimmune diseases and other major disorders. Further studies are needed to elucidate the regulatory role of Sema7A and its variants.