Increased adhesion molecule and chemokine receptor expression on CD8 + T cells trafficking to cerebrospinal fluid in HIV-1 infection

Barbara Shacklett, Catherine A. Cox, David T. Wilkens, R. Karl Karlsson, Annelie Nilsson, Douglas F. Nixon, Richard W. Price

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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 [α4β1 integrin] and leukocyte function antigen [LFA]-1 [αLβ2 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-4high, 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.

Original languageEnglish (US)
Pages (from-to)2202-2212
Number of pages11
JournalJournal of Infectious Diseases
Volume189
Issue number12
DOIs
StatePublished - Jun 15 2004

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Chemokine Receptors
Virus Diseases
Cerebrospinal Fluid
HIV-1
T-Lymphocytes
HLA Antigens
Central Nervous System
Integrins
Chemokine CXCL10
Lymphocytes
Integrin alpha4beta1
Proteins
Capillary Permeability
Lymphocyte Activation
adhesion receptor
Chemokines
Cell Movement
Flow Cytometry
Color
Viruses

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Increased adhesion molecule and chemokine receptor expression on CD8 + T cells trafficking to cerebrospinal fluid in HIV-1 infection. / Shacklett, Barbara; Cox, Catherine A.; Wilkens, David T.; Karlsson, R. Karl; Nilsson, Annelie; Nixon, Douglas F.; Price, Richard W.

In: Journal of Infectious Diseases, Vol. 189, No. 12, 15.06.2004, p. 2202-2212.

Research output: Contribution to journalArticle

Shacklett, Barbara ; Cox, Catherine A. ; Wilkens, David T. ; Karlsson, R. Karl ; Nilsson, Annelie ; Nixon, Douglas F. ; Price, Richard W. / Increased adhesion molecule and chemokine receptor expression on CD8 + T cells trafficking to cerebrospinal fluid in HIV-1 infection. In: Journal of Infectious Diseases. 2004 ; Vol. 189, No. 12. pp. 2202-2212.
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AU - Cox, Catherine A.

AU - Wilkens, David T.

AU - Karlsson, R. Karl

AU - Nilsson, Annelie

AU - Nixon, Douglas F.

AU - Price, Richard W.

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N2 - 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 [α4β1 integrin] and leukocyte function antigen [LFA]-1 [αLβ2 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-4high, 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.

AB - 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 [α4β1 integrin] and leukocyte function antigen [LFA]-1 [αLβ2 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-4high, 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.

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