TY - JOUR

T1 - The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

AU - Hey, A S

AU - Theander, T G

AU - Hviid, L

AU - Hazrati, S M

AU - Kemp, M

AU - Kharazmi, A

N1 - Keywords: Animals; Antibodies, Monoclonal; Antigens, CD4; Binding, Competitive; CD4-Positive T-Lymphocytes; Humans; Leishmania donovani; Leishmania major; Metalloendopeptidases; Protozoan Proteins

PY - 1994

Y1 - 1994

N2 - The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4 Abs to human T cells, whereas the binding of one Ab, OKT4, was not inhibited. Heat inactivation of the protease before the incubation with cells abolished the effect on binding of anti-CD4 Abs. Cells incubated for 2 h with the protease and subsequently washed free of the protease showed a gradual re-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against 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 purified form and in the form anchored to the parasite membrane, cleaves 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 thus disease progression in Leishmania infections.

AB - The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4 Abs to human T cells, whereas the binding of one Ab, OKT4, was not inhibited. Heat inactivation of the protease before the incubation with cells abolished the effect on binding of anti-CD4 Abs. Cells incubated for 2 h with the protease and subsequently washed free of the protease showed a gradual re-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against 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 purified form and in the form anchored to the parasite membrane, cleaves 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 thus disease progression in Leishmania infections.

M3 - Journal article

C2 - 7908919

VL - 152

SP - 4542

EP - 4548

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -