Modulation of lymphocyte interaction with endothelium and homing by HIV-1 gp120.
We have previously shown that HIV-1 glycoprotein 120 (gp120) induces CD4 association with several molecules on the surface of CD4+ lymphocytes. Since one of these molecules was CD38, involved in lymphocyte/endothelium interaction, this article examines the possibility that gp120/CD4 binding alters CD4+ T cell interaction with vascular endothelium in vitro and in vivo. Cocapping experiments showed that gp120 induced CD4 association with CD38, CD29, CD49d, and CD11a in peripheral blood CD4+ T cells. Two in vitro binding assays were used to evaluate the effect of gp120. A static binding assay, performed at 37 degrees C, evaluated stable interactions mediated by integrins, and a dynamic binding assay, performed at 4 degrees C on a rocking shelf, evaluated weak interactions mediated by constitutively active molecules such as selectins and CD38. Gp120 increased dynamic binding and inhibited static binding to the endothelium of peripheral blood CD4+ T cells and SUPT-1 cells. Binding inhibition with mAbs suggested that the gp120 effect on dynamic binding involved CD38, CD31, and CD49d, whereas the effect on static binding involved CD11a and CD49d. In vivo experiments showed that treatment of 2D4 cells, a CD4- CD8- mouse T cell clone transfected with the human CD4, with gp120 increased their homing into the spleen, intestine, and mesenteric lymph nodes, whereas it decreased homing into peripheral lymph nodes. Alteration of lymphocyte homing may contribute to immune deficiency in HIV-1+ patients by decreasing the probability of an encounter between Ags and lymphocytes and inhibiting the spread of effector lymphocytes into tissues.
Bragardo
M
M
Dipartimento di Scienze Mediche, Università di Torino at Novara, Italy.
Buonfiglio
D
D
Feito
M J
MJ
Bonissoni
S
S
Redoglia
V
V
Rojo
J M
JM
Ballester
S
S
Portoles
P
P
Garbarino
G
G
Malavasi
F
F
Dianzani
U
U
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice
D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120