CD6 modulates thymocyte selection and peripheral T cell homeostasis
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AuthorOrta Mascaró, Marc; Consuegra Fernández, Marta; Carreras, Esther; Roncagalli, Romain; Carreras Sureda, Amado; Álvarez Sainz de la Maza, Pilar; Girard, Laura; Simoes, Inés; Martínez Florensa, Mario; Aranda, Fernando; Merino Pérez, Ramón; Martínez, Vanesa-Gabriela; Vicente, Rubén; Merino Pérez, Jesús; Sarukhan, Adelaida; Marissen, Marie; Malissen, Bernard; Lozano, Francisco
The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6(-/-) thymi showed a reduction in both CD4(+) and CD8(+) single-positive subsets, and double-positive thymocytes exhibited increased Ca(2+) mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6(-/-) T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6(-/-) mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4(+)TEM and CD8(+)TCM) and regulatory (T reg) T cells. The suppressive activity of CD6(-/-) T reg cells was diminished, and CD6(-/-) mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells.