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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Front+Immunol 2017 ; 8 (ä): ä Nephropedia Template TP
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Apoptosis Induced via Gamma Delta T Cell Antigen Receptor ?Blocking? Antibodies: A Cautionary Tale #MMPMID28713391
Dutta I; Postovit LM; Siegers GM
Front Immunol 2017[]; 8 (ä): ä PMID28713391show ga
Mechanistic studies contribute greatly to our understanding of ?? T cell (??Tc) biology, aiding development of these cells as immunotherapeutic agents. The antibody blocking assay is an accepted method to determine the receptors involved in ??Tc killing of tumor targets. Effectors and/or targets are preincubated with microgram quantities of monoclonal antibodies (mAb), often described by commercial sources to be useful for blocking assays. We and others have used such assays extensively in the past, correlating decreases in cytotoxicity against specific targets with involvement of the blocked receptor(s). However, we wondered whether other mechanisms might be at play beyond cytotoxicity inhibition. Indeed, administration of certain ?blocking? mAb to the ?? T cell antigen receptor (??TCR) induced ??Tc death. Upon further investigation, we discovered that ??Tc underwent apoptosis triggered by incubation with mAb to the ??TCR. This effect was specific, as no apoptosis was observed when ?? T cells (??Tc) were incubated with these mAb. Apoptosis was further potentiated by the presence of interleukin (IL)-2, often included in cytotoxicity assays; however, exogenous interleukin-2 (IL-2) did not contribute significantly to ??Tc cytotoxicity against breast cancer cell lines. Here, we have investigated the usefulness of four mAb for use in blocking assays by assessing blocking properties in conjunction with their propensity to induce apoptosis in cultured primary human ??Tc. We found that the 5A6.E9 clone was usually a better alternative to the commonly used B1 (or B1.1) and 11F2 clones; however, some variability in susceptibility to apoptosis induction was observed among donor cultures. Thus, viability assessment of primary effector cells treated with mAb alone should be undertaken in parallel with cytotoxicity assays employing blocking antibodies, to account for cytotoxicity reduction caused by effector cell death. Previous findings should be reassessed in this light.