TREATMENT WITH ANTI-LFA-1-ALPHA MONOCLONAL-ANTIBODY SELECTIVELY INTERFERES WITH THE MATURATION OF CD4(-)8(+) THYMOCYTES

Maturation of T lymphocytes in the thymus is driven by signals provide d by soluble factors and by the direct interaction between thymocytes and stromal cells. Although the interaction between T-cell receptor (T CR) and major histocompatibility complex (MHC) molecules on stromal ce lls 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-specifi c monoclonal antibodies. The effect of this treatment on thymocyte sub populations and the expression of CD3 and TCR-alpha beta by these cell s was investigated by flow cytometry. Our data demonstrated that the e ffective saturation of LFA-1 alpha chain in the thymus, but not ICAM-1 or LFA-1 beta chain, selectively interfered with the maturation of CD 8(+) T cells, as manifested by a marked reduction in the frequency of CD4(-)8(+) thymocytes expressing high levels of CD3 and TCR-alpha beta . This selective reduction was also observed in peripheral blood monon uclear cells and spleen cells. The analysis of the frequencies of vari ous V beta TCR showed that CD4(-)8(+) thymocytes were globally affecte d by the treatment. These results underline the importance of the inte raction between LFA-1 and its ligands in the maturation of CD8(+) T ce lls and document the existence of different molecular requirements for the differentiation of CD4(+) and CD8(+) T cells.