Inflammatory bowel disease (IBD) is characterized by an aberrant immune response against microbiota. It is well established that T cells play a critical role in mediating the pathology. Assessing the contribution of each subset of T cells in mediating the pathology is crucial in order to design better therapeutic strategies. This protocol presents a method to identify the specific effector T-cell population responsible for intestinal immunopathologies in bone marrow-engrafted mouse models. Here, we used anti-CD4 and anti-CD8beta depleting antibodies in bone marrow-engrafted mouse models to identify the effector T-cell population responsible for intestinal damage in a genetic mouse model of chronic intestinal inflammation. Key features * This protocol allows addressing the role of CD4+ or CD8alphabeta+ in an engrafted model of inflammatory bowel disease (IBD). * This protocol can easily be adapted to address the role of other immune cells or molecules that may play a role in IBD.