Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vgamma9Vdelta2 naive, memory and effector T cell subsets.
We have compared four human subsets of Vgamma9Vdelta2 T cells, naive (T(naive), CD45RA(+)CD27(+)), central memory (T(CM), CD45RA(-)CD27(+)), effector memory (T(EM), CD45RA(-)CD27(-)) and terminally differentiated (T(EMRA), CD45RA(+)CD27(-)), for their capacity to proliferate and differentiate in response to antigen or homeostatic cytokines. Cytokine responsiveness and IL-15R expression were low in T(naive) cells and progressively increased from T(CM) to T(EM) and T(EMRA) cells. In contrast, the capacity to expand in response to antigen or cytokine stimulation showed a reciprocal pattern and was associated with resistance to cell death and Bcl-2 expression. Whereas antigen-stimulated cells acquired a T(CM) or T(EM) phenotype, IL-15-stimulated cells maintained their phenotype, with the exception of T(CM) cells, which expressed CD27 and CD45RA in various combinations. These results, together with ex vivo bromodeoxyuridine incorporation experiments, show that human Vgamma9Vdelta2 memory T cells have different proliferation and differentiation potentials in vitro and in vivo and that T(EMRA) cells are generated from the T(CM) subset upon homeostatic proliferation in the absence of antigen.
Caccamo
Nadia
N
Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
Meraviglia
Serena
S
Ferlazzo
Viviana
V
Angelini
Daniela
D
Borsellino
Giovanna
G
Poccia
Fabrizio
F
Battistini
Luca
L
Dieli
Francesco
F
Salerno
Alfredo
A
D000941:Antigens / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D000941:Antigens; D016207:Cytokines; C508024:IL15RA protein, human; D019409:Interleukin-15; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens