CD40 ANTIGEN IS EXPRESSED BY ENDOTHELIAL-CELLS AND TUMOR-CELLS IN KAPOSIS-SARCOMA

The CD40 antigen is a member of the tumor necrosis factor receptor/ner ve growth factor receptor superfamily an is involved in cell prolifera tion, differentiation, and survival. Using different monoclonal antibo dies, we found CD40 expression by immunohistochemistry on CD31-and CD3 4-positive Kaposi's sarcoma spindle cells in all tumors of 18 HIV-1 se ropositive and 4 HIV-1 seronegative patients. Western blot analysis of tumor lysates detected a 48- to 50-kd glycoprotein corresponding to t he CD40 antigen expressed by B lymphocytes. CD40 expression was also d etectable in one of four cultures of spindle cells derived from Kaposi sarcoma tissue. Treatment of the CD40-positive spindle cells but not of the CD40-negative ones with interferon-gamma up-regulated CD40 surf ace expression. Besides on Kaposi sarcoma tumor cells, CD40 was distin ctly present on vascular endothelial cells in areas within and adjacen t to the tumors and in benign inflammatory lesions such as granulation tissue of HIV-1-negative patients. In contrast, Cd34-negative endothe lia of thin walled vessels, most likely lymphatics, were predominantly CD40 negative. Only faint or no CD40 expression was found on endothel ial cells in normal skin. We conclude from our data that expression of the Cd40 antigen by endothelial cells is up-regulated during tissue i nflammation. As signaling through CD40 is able to increase cell surviv al, expression of CD40 by Kaposi sarcoma tumor cells might play an imp ortant role in the pathogenesis of this neoplasm.