Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients

• Published in: Blood Vol. 109; no. 9; pp. 3649 - 3657
• Main Authors: Lécureuil, Cédric, Combadière, Béhazine, Mazoyer, Elodie, Bonduelle, Olivia, Samri, Assia, Autran, Brigitte, Debré, Patrice, Combadière, Christophe
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.2007; The Americain Society of Hematology
• Subjects: Adult; Apoptosis - immunology; Biological and medical sciences; Cell Movement - immunology; Disease Progression; Female; Hematologic and hematopoietic diseases; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; Human viral diseases; Humans; Immunologic Memory; Infectious diseases; Interleukin-2 - immunology; Interleukin-2 - metabolism; Male; Medical sciences; Receptors, CCR6; Receptors, CCR7; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - immunology; Spleen - immunology; Spleen - metabolism; Spleen - pathology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Spleen; Immunopathology; Hematology; AIDS; Chemokine receptor; CC chemokine; Immune deficiency; Memory lymphocyte; Infection; Trapping; Cell death; CCR6 chemokine receptor; Viral disease; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-01-035717

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-α 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.