First Author | Bose TO | Year | 2014 |
Journal | J Immunol | Volume | 193 |
Issue | 6 | Pages | 2863-72 |
PubMed ID | 25108025 | Mgi Jnum | J:244645 |
Mgi Id | MGI:5913424 | Doi | 10.4049/jimmunol.1301820 |
Citation | Bose TO, et al. (2014) CD11a is essential for normal development of hematopoietic intermediates. J Immunol 193(6):2863-72 |
abstractText | The process of lymphopoiesis begins in the bone marrow (BM) and requires multiple cellular intermediates. For T cell production, lymphoid progenitors exit the BM and home to the thymus where maturation and selection ensue. These processes are dependent on a number of factors, including chemokines and adhesion molecules. Although the beta2 integrin CD11a plays an important role in the migration of lymphocytes to lymph nodes, the role of CD11a in T cell development is largely undefined. Our studies now show that, in CD11a(-/-) mice, thymic cellularity was decreased and early T cell development was partially impaired. Remarkably, CD11a was critical for generation of common lymphoid progenitors (CLPs) and lymphoid-primed multipotent progenitors. However, in intact CD11a(-/-) mice, peripheral B and T cell subsets were only modestly altered, suggesting that compensatory mechanisms were operating. In contrast, competitive BM-reconstitution assays revealed an essential role for CD11a in the generation of thymocytes and mature T and B cells. This defect was linked to the requirement for CD11a in the development of CLPs. Furthermore, our results identified CLPs, and not lymphoid-primed multipotent progenitors, as the requisite CD11a-dependent precursor for lymphocyte development. Thus, these findings established a key role for CD11a in lymphopoiesis. |