Increased adhesion molecule and chemokine receptor expression on CD8+ T cells trafficking to cerebrospinal fluid in HIV-1 infection.
BACKGROUND
The central nervous system (CNS) is a recognized target for human immunodeficiency virus type 1 (HIV-1). CD8(+) T cells may mediate viral clearance from the CNS but also may contribute to immune-mediated neuronal damage.


METHODS
Using 4- and 6-color flow cytometry, we investigated the role of adhesion molecules (very late antigen [VLA]-4 [ alpha 4 beta 1 integrin] and leukocyte function antigen [LFA]-1 [ alpha L beta 2 integrin]) and chemokine receptors (CXCR3 and CCR5) in CD8(+) T cell migration to cerebrospinal fluid (CSF) during HIV-1 infection.


RESULTS
CD8(+) T cells trafficking to CSF were uniformly VLA-4(high), LFA-1(high). CCR5 expression was significantly enhanced in T cells from CSF, compared with those from blood (P<.001), including HIV-1-specific CD8(+) T cells, and most T cells from CSF expressed both CXCR3 and CCR5. Interferon-inducible protein (IP)-10 (CXCL10) levels in CSF were significantly increased in HIV-1-positive individuals, relative to IP-10 levels in control subjects (P=.007), and a positive correlation was found between IP-10 levels and virus load in CSF (r2=.777; P=.0007).


CONCLUSIONS
These findings suggest that LFA-1, CCR5 and CXCR3, and IP-10 play an important role in lymphocyte trafficking to CSF during HIV-1 infection. These observations suggest a "push-pull" model, in which lymphocyte extravasation is driven by lymphocyte activation, expression of adhesion molecules, and increased vascular permeability and is coupled with chemokine-mediated trafficking to inflammatory sites in the CNS.
Shacklett
Barbara L
BL
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California, USA. blshacklett@ucdavis.edu.
Cox
Catherine A
CA
Wilkens
David T
DT
Karl Karlsson
R
R
Nilsson
Annelie
A
Nixon
Douglas F
DF
Price
Richard W
RW
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology* / Q000821:virology; D002634:Chemotaxis, Leukocyte; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D007964:Leukocytosis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D015854:Up-Regulation
C515187:CXCR3 protein, human; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine