Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue.
OBJECTIVE
To examine compartmental differences in co-receptor expression on CD4 lymphocytes between blood and gut using endoscopic biopsies.


METHODS
Mucosal and peripheral CD4 T cells from healthy controls were compared for co-receptor expression and vulnerability to infection by HIV-1.


METHODS
Expression of CCR5 and CXCR4 was quantified by flow cytometry on isolated mucosal CD4 lymphocytes obtained from endoscopic biopsies and blood from healthy controls. Vulnerability to in vitro infection by both R5 and X4 strains was assessed by measuring p24.


RESULTS
Biopsies yielded sufficient lymphocytes for flow cytometric characterization and infectivity studies. The percentage of mucosal CD4 T lymphocytes that expressed CCR5 and the per cell expression of CCR5 were both significantly increased compared with that in peripheral blood CD4 T lymphocytes. CXCR4 was expressed on the majority of CD4 lymphocytes in both compartments. In vitro infection of mucosal mononuclear cells supported greater viral replication of both R5 and X4 strains than peripheral blood mononuclear cells.


CONCLUSIONS
Enhanced expression of CXCR4 and CCR5 on CD4 lymphocytes in normal intestinal mucosa predicts increased vulnerability to infection by both R5 and X4 HIV-1. Endoscopic biopsies provide a useful mucosal tissue sampling technique to identify compartmental immunologic differences that may be exploited by HIV-1 in establishing initial mucosal infection.
Anton
P A
PA
Center for HIV and Digestive Diseases, Division of Digestive Diseases, UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California, USA.
Elliott
J
J
Poles
M A
MA
McGowan
I M
IM
Matud
J
J
Hultin
L E
LE
Grovit-Ferbas
K
K
Mackay
C R
CR
Chen ISY
Giorgi
J V
JV
D001706:Biopsy; D015704:CD4 Antigens / Q000378:metabolism; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D013997:Time Factors
D015704:CD4 Antigens; D016655:HIV Core Protein p24; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV