Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients.
CCR6, a homeostatic chemokine receptor, is shown here to characterize subsets of both central and effector memory T cells that secrete high levels of IL-2 and TNF-alpha in response to polyclonal and antigen-specific stimulation. CCR6(+) T lymphocytes disappeared dramatically from the peripheral blood of HIV-infected patients as HIV disease progressed. The capacity of CD4(+)CCR6(+) to secrete multiple cytokines remained intact among HIV-infected long-term nonprogressors but was partially lost from subjects with standard disease progression. CCR6(+) T lymphocytes, regardless of their CCR7 expression, accumulated in the spleen of HIV-infected patients, where they died by apoptosis. Assessment of CCR6 expression allowed us to describe novel memory T-cell subpopulations capable of high cytokine production and provided evidence of a pathologic CCR6-dependent pathway of memory T-cell homing that may participate in the loss of memory response against infections.
Lécureuil
Cédric
C
INSERM U543, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine, Université Pierre et Marie Curie-Paris 6, Paris, France.
Combadière
Béhazine
B
Mazoyer
Elodie
E
Bonduelle
Olivia
O
Samri
Assia
A
Autran
Brigitte
B
Debré
Patrice
P
Combadière
Christophe
C
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008297:Male; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
C106311:CCR6 protein, human; C515370:CCR7 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine