B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction.
B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or down-modulate T-cell responses. Although it was shown that B7-H3 could inhibit T-cell responses, several studies - most of them performed in murine systems - found B7-H3 to act in a costimulatory manner. In this study, we have specifically addressed a potential functional dualism of human B7-H3 by assessing the effect of this molecule under varying experimental conditions as well as on different T-cell subsets. We show that B7-H3 does not costimulate human T cells. In the presence of strong activating signals, B7-H3 potently and consistently down-modulated human T-cell responses. This inhibitory effect was evident when analysing proliferation and cytokine production and affected naïve as well as pre-activated T cells. Furthermore, we demonstrate that B7-H3-T-cell interaction is characterised by an early suppression of IL-2 and that T-cell inhibition can be reverted by exogenous IL-2. Since the triggering receptor expressed on myeloid cells like transcript 2 (TREML2/TLT-2) has been recently described as costimulatory receptor of murine B7-H3 we have extensively analysed interaction of human B7-H3 with TREML2/TLT-2. In these experiments we found no evidence for such an interaction. Furthermore, our data do not point to a role for murine TREML2 as a receptor for murine B7-H3.
Leitner
Judith
J
Institute of Immunology, Center of Physiology, Pathophysiology and Immunology, Medical University Vienna, Austria.
Klauser
Christoph
C
Pickl
Winfried F
WF
Stöckl
Johannes
J
Majdic
Otto
O
Bardet
Anaïs F
AF
Kreil
David P
DP
Dong
Chen
C
Yamazaki
Tomohide
T
Zlabinger
Gerhard
G
Pfistershammer
Katharina
K
Steinberger
Peter
P
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; C486038:Cd276 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D011971:Receptors, Immunologic; C473367:TREML2 protein, human