Program: Oral and Poster Abstracts
Session: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion and Stromal Stem Cells: Poster II
To examine the role of LFA-1-mediated adhesion to stromal cells or adjacent hematopoietic precccursors in early lymphoid differentiation, we examined the effect of anti-LFA-1 blocking antibody (Ab) on the differentiation of CD34+CD45RA-CD7-CD10-CD38lo/- hematopoietic precursors in the cultures on stromal cells or with conditioned medium (CM) obtained from cultures of stromal cells. In the cultures on stromal cells, anti-LFA-1 Ab strongly inhibited the generation of CD7+CD10-CD45RA+ and CD7-CD10+CD45RA+ lymphoid precursors from hematopoietic precursors after 21 days of culture. Significant number of CD14+monocytic cells was generated with or without anti-LFA-1 Ab. In the cultures with CM, anti-LFA-1 Ab showed marginable effect on lymphoid differentiation. To elucidate the effect of anti-LFA-1 Ab on more mature lymphoid precursors, CD7+CD10-CD45RA+ or CD7-CD10+CD45RA+ cells were isolated after culture of hematopoietic cells for 14 days and cultured on stromal cells in the presence or absence of anti-LFA-1 Ab. Anti-LFA-1 Ab remarkably inhibited the generation of CD7+ and CD10+CD19+ lymphoid cells from the CD7+CD10-CD45RA+ early T-lymphoid precursors. Notably, few or no CD45RA+CD14- lymphoid cells were detected. Anti-LFA-1 Ab did not affect B-lineage differentiation from CD10+CD19-CD45RA+ early B-lymphoid precursors to CD10+CD19+CD45RA+proB cells. We next examined which ICAM ligand is responsible for the observed effects by anti-LFA-1 Ab. Anti-ICAM-2 Ab inhibited the generation of CD7+CD45RA+ and CD10+CD45RA+ lymphoid precursors from CD34+CD45RA-CD7-CD10-CD38lo/- hematopoietic precursors on stromal cells, as observed with anti-LFA-1 Ab. No effect was observed with anti-ICAM-1 Ab. Anti-ICAM-2 Ab further suppressed the generation of CD7+ and CD10+ lymphoid cells from the cultured CD7+CD10-CD45RA+ early T-lymphoid precursors, but did not depress B-lymphoid differentiation from the cultured CD7-CD10+CD45RA+ early B-lymphoid precursors.
Taken together, these data indicate that LFA-1-mediated adhesion to ICAM-2 is essential for stromal cell-dependent early lymphoid differentiation of hematopoietic and CD7+ early T-lymphoid precursors.
Disclosures: No relevant conflicts of interest to declare.
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