Increased Adhesion Molecule and Chemokine Receptor Expression on CD8 + T Cells Trafficking to Cerebrospinal Fluid in HIV‐1 Infection

• Published in: The Journal of infectious diseases Vol. 189; no. 12; pp. 2202 - 2212
• Main Authors: Shacklett, Barbara L., Cox, Catherine A., Wilkens, David T., Karl Karlsson, R., Nilsson, Annelie, Nixon, Douglas F., Price, Richard W.
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 15.06.2004; Oxford University Press
• Subjects: Adult; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Adhesion Molecules - metabolism; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - immunology; Cerebrospinal Fluid - virology; Chemotaxis, Leukocyte; Female; Fundamental and applied biological sciences. Psychology; HIV Infections - immunology; HIV Infections - physiopathology; HIV Infections - virology; HIV-1 - pathogenicity; Human viral diseases; Humans; Infectious diseases; Integrin alpha4beta1 - metabolism; Leukocytosis; Lymphocyte Function-Associated Antigen-1 - metabolism; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Receptors, CCR5 - metabolism; Receptors, Chemokine - metabolism; Receptors, CXCR3; Up-Regulation; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Immunopathology; T cell receptor; Microbiology; HIV-1 virus; Retroviridae; AIDS; Chemokine receptor; Cerebrospinal fluid; Immune deficiency; Lentivirus; Adhesion; Virus; Infection; Viral disease; T-Lymphocyte; Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/421244

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. 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. 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). 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.