title: Cell-to-cell interactions and signals involved in the reconstitution of peripheral CD8 T(CM) and T(EM) cell pools.
abstract: We here describe novel aspects of CD8(+) and CD4(+) T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8(+) T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8(+) T cells and their differentiation of effector functions is limited, but both dramatically increase upon the co-transfer of CD4(+) T cells. This helper effect is complex and determined by multiple factors. It was directly correlated to the number of helper cells, required the continuous presence of the CD4(+) T cells, dependent on host antigen-presenting cells (APCs) expressing CD40 and on the formation of CD4/CD8/APC cell clusters. By comparing the recovery of (CD44(+)CD62L(high)) T(CM) and (CD44(+)CD62L(low)) T(EM) CD8(+) T cells, we found that the accumulation of T(CM) and T(EM) subsets is differentially regulated. T(CM)-cell accumulation depended mainly on type I interferons, interleukin (IL)-6, and IL-15, but was independent of CD4(+) T-cell help. In contrast, T(EM)-cell expansion was mainly determined by CD4(+) T-cell help and dependent on the expression of IL-2Rβ by CD8 cells, on IL-2 produced by CD4(+) T-cells, on IL-15 and to a minor extent on IL-6.
authors.affiliation: Lymphocyte Population Biology Unit, CNRS, URA 1961, Institut Pasteur, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Zaragoza
authors.forename: César
authors.initials: C
authors.lastname: Evaristo
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Valentina
authors.initials: V
authors.lastname: Libri
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Benedita
authors.initials: B
authors.lastname: Rocha
authors.forename: António A
authors.initials: AA
authors.lastname: Freitas
authors.forename: Afonso R M
authors.initials: AR
authors.lastname: Almeida
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D019713:Receptors, CCR5 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D013997:Time Factors
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D019713:Receptors, CCR5; D023201:CD40 Ligand