| CD6 modulates the threshold for thymocyte selection and peripheral T cell homeostasis. | | CD6 modulates the threshold for thymocyte selection and peripheral T cell homeostasis. | M. Orta-Mascaró, M. Consuegra-Fernández, E. Carreras, R. Roncagalli, A. Carreras-Sureda, P. Alvarez, L. Girard, I. Simões, M. Martínez-Florensa, F. Aranda, R. Merino, V. G. Martínez, R. Vicente, J. Merino, A. Sarukhan, M. Malissen, B. Malissen and F. Loza | 2016-06-30T22:00:00Z | <p><strong class="ms-rteFontSize-2" style="text-align:justify;">Abstract</strong></p><p style="text-align:justify;"><span class="ms-rteFontSize-2">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/ALC AM (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</span><sup class="ms-rteFontSize-2">-</sup><sup class="ms-rteFontSize-2">/</sup><sup class="ms-rteFontSize-2">-</sup><span class="ms-rteFontSize-2">thymi showed a reduction in both CD4</span><sup class="ms-rteFontSize-2">+</sup><span class="ms-rteFontSize-2">and CD8</span><sup class="ms-rteFontSize-2">+</sup><span class="ms-rteFontSize-2">single-positive subsets, and double-positive thymocytes exhibited increased Ca</span><sup class="ms-rteFontSize-2">2+</sup><span class="ms-rteFontSize-2">mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6</span><sup class="ms-rteFontSize-2">-</sup><sup class="ms-rteFontSize-2">/</sup><sup class="ms-rteFontSize-2">-</sup><span class="ms-rteFontSize-2">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</span><sup class="ms-rteFontSize-2">-</sup><sup class="ms-rteFontSize-2">/</sup><sup class="ms-rteFontSize-2">-</sup><span class="ms-rteFontSize-2">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</span><sup class="ms-rteFontSize-2">+</sup><span class="ms-rteFontSize-2">T</span><sub class="ms-rteFontSize-2">EM</sub><span class="ms-rteFontSize-2">and CD8</span><sup class="ms-rteFontSize-2">+</sup><span class="ms-rteFontSize-2">T</span><sub class="ms-rteFontSize-2">CM</sub><span class="ms-rteFontSize-2">) and regulatory (T reg) T cells. The suppressive activity of CD6</span><sup class="ms-rteFontSize-2">-</sup><sup class="ms-rteFontSize-2">/</sup><sup class="ms-rteFontSize-2">-</sup><span class="ms-rteFontSize-2">T reg cells was diminished, and CD6</span><sup class="ms-rteFontSize-2">-</sup><sup class="ms-rteFontSize-2">/</sup><sup class="ms-rteFontSize-2">-</sup><span class="ms-rteFontSize-2">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.</span><br></p> | <p><span class="ms-rteFontSize-2"></span></p><p><span class="ms-rteFontSize-2"><a href="https://www.ncbi.nlm.nih.gov/pubmed/27377588">J. Exp. Med. 2016, 213: 1387-1397. doi: 10.1084/jem.20151785.</a></span></p> | 166 | | |
