Skewed representation of functionally distinct populations of Vgamma9Vdelta2 T lymphocytes in aging.
We recently demonstrated that numerical and functional alterations of gammadelta T cells are present in healthy elderly. Here we observed that the decreased absolute number of Vgamma9Vdelta2 T cells present in old subjects in comparison with young/adult and middle aged donors is due to the reduction of naive and central memory Vgamma9Vdelta2 T cells bearing CD27 and CCR7 antigens. The proportion of effector/memory Vgamma9Vdelta2 T cells lacking CD27 or CCR7 markers was significantly increased in the peripheral blood of old subjects in comparison with younger donors. Moreover, the percentage of CD69+ gammadelta T cells was significantly increased in old subjects in comparison with younger donors after overnight activation, confirming that more effector cells are available in aged people. A functional analysis in young/adult and middle aged donors revealed that effector/memory CD27- Vgamma9Vdelta2 T cells are increased after 10-days of in vitro colture in the presence of isopentenylpyrophosphate (IPP) and IL-2. In contrast, the IPP+IL-2 mediated differentiation and expansion of CD27- effector/memory cells was absent in old subjects, confirming a lack of naive and central memory cells responding to IL-2. Accordingly, the expansion index of effector/memory CD27- Vgamma9Vdelta2 T cells was negatively correlated with the donor age. Finally, terminally differentiated Vgamma9Vdelta2 T cells measured as perforin content after 10-day in vitro expansion showed no age-related difference. These data demonstrated a shift of the circulating gammadelta T cell population towards CD27- and CCR7- effector T cells in the elderly with the reduction of immature CD27+ and CCR7+ T cell precursors.
Re
Francesca
F
Laboratory of Tumor Immunology, Immunology Center, Italian National Research Center on Aging (INRCA), Via Birarelli 8, 60121 Ancona, Italy.
Poccia
Fabrizio
F
Donnini
Alessia
A
Bartozzi
Beatrice
B
Bernardini
Giovanni
G
Provinciali
Mauro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D045782:Hemiterpenes / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D045782:Hemiterpenes; D007376:Interleukin-2; D037181:Lectins, C-Type; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000099192:CD69 Antigens; C515370:CCR7 protein, human; C004809:isopentenyl pyrophosphate