LFA-1 Knockout Leads to CD4 + and CD8 + T Cells Differentiation Disorder in Thymus Gland and is Related with ERK Signaling Pathway in Mice

Abstract T cell precursors from fetal liver bone marrow migrate into the thymus to initiate their development, including double-negative selection, double-positive selection, and single-positive selection. Subsequently, fully matured single-positive CD4+ T cells or CD8+ T cells traverse the bloodstream to the peripheral tissues, executing immune functions. Lymphocyte function-associated antigen-1 (LFA-1) is invovuled with thymic cortical epithelial cells facilitate positive selection. But LFA-1 mediates signaling pathways in thymic keep unknown. Here, Knockout LFA-1 displayed thymic atrophy and aberrant structural alterations in the cortical and medullary of the thymus in mice. And the cells populations of thymocytes during the positive and negative selection process was observed, characterized by CD4+ T cells increased and CD8+ T cells decreased. Furthermore, LFA-1 inhibitor also impact on thymic development. A significant downregulation of pERK1/2 in MAPK signaling pathway. The thymus gland medullary atrophy still was observed in LFA-1 knockout mice with tail vein tumor metastasis, along with CD4+ T lymphocytes increased and a reduced CD8+ T cells. The Genome Databases revealed that mutations in LFA-1 in clinical patients, suggesting that LFA-1 mutation individuals maybe affect the CD8+ T cells function. This study indicated that LFA-1 regulates the differentiation of CD4+ T and CD8+ T cells in the thymus, implying that LFA-1 mutation in health individuals may influence the tumor immunity or therapy when they get tumor.