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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1678-1686
CHEMOKINES
Deregulation of the expression of the fractalkine/fractalkine
receptor complex in HIV-1-infected patients
Arnaud Foussat,
Laurence Bouchet-Delbos,
Dominique Berrebi,
Ingrid Durand-Gasselin,
Aurore Coulomb-L'Hermine,
Roman Krzysiek,
Pierre Galanaud,
Yves Levy, and
Dominique Emilie
From INSERM U131, Department of Pathology, Department
of Internal Medicine and Clinical Immunology, Antoine
Béclère Hospital, Paris-South Institute on Cytokines,
Clamart, France; Department of Pathology, UPRESA 3102, Robert
Debré Hospital, Paris, France; Department of Clinical Immunology,
Henri Mondor Hospital, Créteil, France.
Fractalkine is the only member of the CX3C chemokine family.
Polymorphism of the fractalkine receptor gene may influence the prognosis of human immunodeficiency virus (HIV) infection, but the
nature of the cells expressing fractalkine or its receptor in
HIV-infected patients remains unknown. We show that, in contrast to
HIV-uninfected individuals, a large number of cells expressed fractalkine in T-cell zones of lymph nodes from HIV-infected patients. CD83+ mature and CD123+ plasmacytoid dendritic
cells as well as plasma cells are involved in this increased expression
of fractalkine. Increased numbers of plasmacytoid dendritic cells and
plasma cells were present in T-cell zones of HIV-infected patients.
CD83+ dendritic cells were present in similar number in
HIV-infected patients and controls, but an increased fraction of these
cells produced fractalkine in HIV-infected patients. Many plasma cells in the gut-associated lymphoid tissue from HIV-infected patients also
produced fractalkine, whereas few cells produced fractalkine in the gut
of controls. The fraction of CD45RO+ and
CD45RO T helper (Th) cells expressing the fractalkine
receptor CX3CR1 was higher in HIV-infected patients than in healthy
individuals, and these cells were abnormally sensitive to fractalkine
stimulation. This increased response correlated with HIV viremia, and
it returned to normal levels in patients successfully treated with
antiretroviral drugs. The increased expression of the
fractalkine/fractalkine receptor complex associated with HIV
infection may affect adhesion and migration of Th lymphocytes and their
interaction with dendritic cells. Thus, it may influence the
equilibrium between depletion and renewal of the Th lymphocyte compartment.
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