title: HIV infection impairs CCR7-dependent T-cell chemotaxis independent of CCR7 expression.
abstract: OBJECTIVE
  CCR7, a chemokine receptor expressed at high levels on naive and central memory T cells, is essential for T-cell recirculation into secondary lymphoid organs. We investigated CCR7 expression and chemotactic function in patient T cells, to gain further insights into mechanisms of T-cell dysfunction in HIV infection.
  
  
  METHODS
  CCR7 expression and function were measured in T-cell subsets of viremic patients (n = 15), efficiently treated patients (n = 12), and healthy blood donors (n = 14). A whole blood assay was developed to measure chemotaxis in unperturbed T cells with physiological chemokine receptor expression levels.
  
  
  RESULTS
  The proportion of CCR7hi T-cell subsets (naive and central memory) was decreased in HIV-infected patients, but the expression of CCR7 within T-cell subsets did not differ from that in healthy controls. In spite of preserved CCR7 expression, CCR7-dependent chemotactic responses were significantly decreased within most T-cell subsets from viremic patients, including naive, central memory, and effector memory CD4 T cells and naive, central memory, and effector CD8 T cells. The chemotaxis defect was only partially corrected in efficiently treated patients. Importantly, chemotaxis to CXCR4, another chemokine receptor involved in T-cell recirculation, was preserved or even increased in T-cell subsets of HIV-infected patients.
  
  
  CONCLUSIONS
  These findings provide evidence for an impairment of CCR7 function in patient T cells, which may have major consequences on T-cell recirculation. The fact that CXCR4 function was preserved points to a CCR7-specific functional defect rather than a general block in chemotaxis.
authors.affiliation: Institut Pasteur, Paris, France.
authors.forename: Santiago
authors.initials: S
authors.lastname: Perez-Patrigeon
authors.forename: Benoît
authors.initials: B
authors.lastname: Vingert
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Viard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Jacques
authors.initials: J
authors.lastname: Thèze
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Chakrabarti
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002908:Chronic Disease; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D012367:RNA, Viral / Q000097:blood; D054400:Receptors, CCR7 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: C515370:CCR7 protein, human; C527276:CXCR4 protein, human; D012367:RNA, Viral; D054400:Receptors, CCR7; D019718:Receptors, CXCR4