Monoclonal antibodies to B and T lymphocyte attenuator (BTLA) have no effect on in vitro B cell proliferation and act to inhibit in vitro T cell proliferation when presented in a cis, but not trans, format relative to the activating stimulusc ei_4259 and T cells and that some antibodies inhibit anti-CD3e-induced T cell proliferation in vitro, but only when constrained appropriately with a putatively cross-linking reagent. The antibodies had no significant effect on in vitro T cell proliferation in a mixed lymphocyte reaction (MLR) assay nor on in vitro DO11.10 antigen-induced T cell proliferation. None of these antibodies, nor HVEM-Fc, had any significant effect on in vitro B cell proliferation induced by anti-immunoglobulin M antibodies (Ïźanti-CD40) or lipopolysaccharide. We further elucidated the requirements for inhibition of in vitro T cell proliferation using a beads-based system to demonstrate that the antibodies that inhibited T cell proliferation in vitro were required to be presented to the T cell in a cis, and not trans, format relative to the anti-CD3e stimulus. We also found that antibodies that inhibited T cell proliferation in vitro had no significant effect on the antibody captured interleukin-2 associated with the in vivo activation of DO11.10 T cells transferred to syngeneic recipient BALB/c mice. These data suggest that there may be specific structural requirements for the BTLA molecule to exert its effect on lymphocyte activation and proliferation. HVEM is also the receptor for both LIGHT and lymphotoxin-a, which bind in the CRD2 and CRD3 domains, and for CD160, which has been reported to compete with BTLA for binding to HVEM [6].
KeywordsFunctionally, several investigators have provided evidence that signalling through BTLA acts to inhibit T lymphocyte proliferation using a transfected cell co-culture system, plateimmobilized HVEM ligand or monoclonal antibodies Clinical and Experimental Immunology ORIGINAL ARTICLE