THE MAJOR SURFACE GLYCOPROTEIN (GP63) FROM LEISHMANIA-MAJOR AND LEISHMANIA-DONOVANI CLEAVES CD4 MOLECULES ON HUMAN T-CELLS

The effect of Leishmania major and L. donovani surface protease gp63 o n surface markers on human T cells was studied using fluorescence-acti vated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at conc entrations above 10 mu g/ml completely inhibited binding of six differ ent anti-CD4 Abs to human T cells, whereas the binding of one Ab, OKT4 , was not inhibited. Heat inactivation of the protease before the incu bation with cells abolished the effect on binding of anti-CD4 Abs. Cel ls incubated for 2 h with the protease and subsequently washed free of the protease showed a gradual re-expression of CD4, reaching 50% of t he initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 compa rable to that seen with purified gp63. The binding of Abs directed aga inst other surface markers present on human T-cells-CD2, CD3, CD5, CD8 , CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ- was not inhibited by gp63. These data suggest that gp63, both in its p urified form and in the form anchored to the parasite membrane, cleave s CD4 on human T cells. The cleavage of CD4 by the protease might play a role in interfering with the induction of the immune response and t hus disease progression in Leishmania infections.