Differential expression of CD97 on human lymphocyte subsets and limited effect of CD97 antibodies on allogeneic T-cell stimulation

CD97 is a large heptahelical EGF-TM7 receptor broadly expressed on hematopoietic cells as three isoforms with respectively three, four, or five epidermal growth factor (EGF)-like domains. We here describe the expression characteristics of CD97 on human lymphocyte subsets. We found CD97 to be present on all lymphocytes in blood and lymphoid tissue. Expression of CD97 on B cells was lower compared to T and NK cells and did not differ between B-cell subsets. In CD4+ T cells, CD97 expression was higher on memory cells compared to naive cells. In CD8+ T and NK cells, we found a downregulation of CD97 on cytolytic effector cells. Stimulation through CD3 and CD28 resulted in a rapid upregulation of CD97 in all T-cell subsets within 2–4 h. A link between CD97 expression and lymphocyte proliferation was established in NK cells, which markedly upregulated CD97 in response to IL-2 and IL-15. Mixed lymphocyte cultures revealed a limited ability of the stalk region-specific monoclonal antibody CLB-CD97/3 to inhibit CD8+ and CD4+ allogeneic T-cell proliferation.