Treatment with anti-LFA-1α monoclonal antibody selectively interferes with the maturation of CD4-8+ thymocytes

Abstract

Maturation of T lymphocytes in the thymus is driven by signals provided by soluble factors and by the direct interaction between thymocytes and stromal cells. Although the interaction between T-cell receptor (TCR) and major histocompatibility complex (MHC) molecules on stromal cells is crucial for T-cell development, other accessory molecules seem to play a role in this process. In order to better understand the role of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) molecules in thymocyte maturation, mice were treated from birth with saturating doses of non-cytolytic-specific monoclonal antibodies. The effect of this treatment on thymocyte subpopulations and the expression of CD3 and TCR-αβ by these cells was investigated by flow cytometry. Our data demonstrated that the effective saturation of LFA-1 chain in the thymus, but not ICAM-1 or LFA-1β chain, selectively interfered with the maturation of CD8+ T cells; as manifested by a marked reduction in the frequency of CD4-8+ thymocytes expressing high levels of CD3 and TCR-αβ. This selective reduction was also observed in peripheral blood mononuclear cells and spleen cells. The analysis of the frequencies of various Vβ TCR showed that CD4-8+ thymocytes were globally affected by the treatment. These results underline the importance of the interaction between LFA-1 and its ligands in the maturation of CD8+ T cells and document the existence of different molecular requirements for the differentiation of CD4+ and CD8+ T cells.