Long-term engagement of CD6 and ALCAM is essential for T cell proliferation induced by dendritic cells. Export

@article{citeulike:562075, abstract = {Interactions between T cells and antigen-presenting cells are the first step in the induction of an adaptive immune response. Here, we show that CD6 and its ligand ALCAM are actively recruited to the antigen-induced DC-T cell contact zone. Moreover, ALCAM-blocking antibodies interfere with DC-T cell conjugate formation, demonstrating that CD6-ALCAM binding is essential for stable T cell-APC contact. We now demonstrate that besides their role in establishing initial contacts, CD6-ALCAM interactions are also required during the proliferative phase of the T cell response; the presence of CD6-blocking antibodies or recombinant ALCAM-Fc proteins results in a strong and sustained inhibition of T cell proliferation. Furthermore, simultaneous crosslinking of CD6 and CD3 induces enhanced proliferation and transcriptional activity to a similar level as observed after CD3 and CD28 co-crosslinking, demonstrating that CD6 is an important co-stimulatory molecule. The stability of ALCAM-CD6 binding, which contrasts with transient homotypic ALCAM-ALCAM interactions, further supports the long-lasting effects observed on T cell proliferation. Taken together, we demonstrate that CD6 and ALCAM form a key adhesive receptor-ligand pair that is not only involved in early DC-T cell binding but also in sustaining DC-induced T cell proliferation long after the initial contact has been established.}, address = {Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Nijmegen, The Netherlands.}, author = {Zimmerman, Aukje W W. and Joosten, Ben and Torensma, Ruurd and Parnes, Jane R R. and van Leeuwen, Frank N N. and Figdor, Carl G G.}, citeulike-article-id = {562075}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2005-09-3881}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16352806}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16352806}, day = {13}, doi = {10.1182/blood-2005-09-3881}, issn = {0006-4971}, journal = {Blood}, keywords = {alcam, cd6, cell, t}, month = {December}, posted-at = {2006-03-24 08:46:58}, priority = {0}, title = {Long-term engagement of CD6 and ALCAM is essential for T cell proliferation induced by dendritic cells.}, url = {http://dx.doi.org/10.1182/blood-2005-09-3881}, year = {2005} }

TY - JOUR ID - citeulike:562075 L3 - citeulike-article-id:562075 N2 - Interactions between T cells and antigen-presenting cells are the first step in the induction of an adaptive immune response. Here, we show that CD6 and its ligand ALCAM are actively recruited to the antigen-induced DC-T cell contact zone. Moreover, ALCAM-blocking antibodies interfere with DC-T cell conjugate formation, demonstrating that CD6-ALCAM binding is essential for stable T cell-APC contact. We now demonstrate that besides their role in establishing initial contacts, CD6-ALCAM interactions are also required during the proliferative phase of the T cell response; the presence of CD6-blocking antibodies or recombinant ALCAM-Fc proteins results in a strong and sustained inhibition of T cell proliferation. Furthermore, simultaneous crosslinking of CD6 and CD3 induces enhanced proliferation and transcriptional activity to a similar level as observed after CD3 and CD28 co-crosslinking, demonstrating that CD6 is an important co-stimulatory molecule. The stability of ALCAM-CD6 binding, which contrasts with transient homotypic ALCAM-ALCAM interactions, further supports the long-lasting effects observed on T cell proliferation. Taken together, we demonstrate that CD6 and ALCAM form a key adhesive receptor-ligand pair that is not only involved in early DC-T cell binding but also in sustaining DC-induced T cell proliferation long after the initial contact has been established. JF - Blood SN - 0006-4971 AD - Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Nijmegen, The Netherlands. TI - Long-term engagement of CD6 and ALCAM is essential for T cell proliferation induced by dendritic cells. KW - alcam KW - cd6 KW - cell KW - t AU - Zimmerman, Aukje W AU - Joosten, Ben AU - Torensma, Ruurd AU - Parnes, Jane R AU - van Leeuwen, Frank N AU - Figdor, Carl G PY - 2005/12/13/ UR - http://dx.doi.org/10.1182/blood-2005-09-3881 ER -