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Activation of effector T cells in tissues is still poorly understood. In fact, it is not known how these cells survive to accomplish their task. We examined if β1-integrins highly expressed on these cells could protect them from apoptosis. Using Jurkat and primary T cells, we studied if ligands of β1-integrins could influence the Fas apoptosic pathway. Our results show that interaction of type I collagen with α2β1 integrin activate the protein phosphatase 2A dependent activation of the MAPK/Erk pathway to protect T cells from Fas-induced apoptosis by blocking procaspase-8 activation. Our results suggest that interaction of T lymphocyte with type I collagen, which is abundant in peripheral tissues, is an important event in the control of T lymphocyte homeostasis and immune response, and could be involve in chronic inflammation.