TY - JOUR
T1 - Human T cell crosstalk is induced by tumor membrane transfer
AU - Uzana, Ronny
AU - Eisenberg, Galit
AU - Merims, Sharon
AU - Frankenburg, Shoshana
AU - Pato, Aviad
AU - Yefenof, Eitan
AU - Engelstein, Roni
AU - Peretz, Tamar
AU - Machlenkin, Arthur
AU - Lotem, Michal
N1 - Publisher Copyright:
© 2015 Uzana et al.
PY - 2015/2/11
Y1 - 2015/2/11
N2 - Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+T-APCs). We demonstrate that, following trogocytosis, CD8+T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response.
AB - Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+T-APCs). We demonstrate that, following trogocytosis, CD8+T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response.
UR - http://www.scopus.com/inward/record.url?scp=84923037149&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0118244
DO - 10.1371/journal.pone.0118244
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C2 - 25671577
AN - SCOPUS:84923037149
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e0118244
ER -