title: Antigen-specific central memory CD4+ T lymphocytes produce multiple cytokines and proliferate in vivo in humans.
abstract: The function of Ag-specific central (T(CM)) and effector (T(EM)) memory CD4+ T lymphocytes remains poorly characterized in vivo in humans. Using CD154 as a marker of Ag-specific CD4+T cells, we studied the differentiation of memory subsets following anti-hepatitis B immunization. Hepatitis B surface Ag (HBs)-specific memory CD4+T cells were heterogeneous and included T(CM) (CCR7+CD27+) and T(EM) (CCR7(-)CD27(+/-)). HBs-specific T(CM) and T(EM) shared the capacity to produce multiple cytokines, including IL-2 and IFN-gamma. Several years postimmunization, approximately 10% of HBs-specific memory CD4+ T cells were in cycle (Ki67+) and the proliferating cells were CCR7+. These results suggest that the model of functional specialization of T(CM) and T(EM) cannot be applied to protein vaccine Ags and support the concept that T(CM) are capable of self-renewal and contribute to maintain the pool of memory cells.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Rue Adrienne Bolland 8, 6041 Charleroi, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Stubbe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vanderheyde
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
chemical_list: C515370:CCR7 protein, human; D016207:Cytokines; C075654:Engerix-B; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D023201:CD40 Ligand