CD4+CD25+ T regulatory cells inhibit cytotoxic activity of CTL and NK cells in humans-impact of immunosenescence.
We hypothesized that advanced age and medical conditions had an impact on the accumulation of CD4+CD25+ T regulatory cells (Treg), which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells. Volunteers were divided according to the Senieur Protocol into healthy young and elderly and non-healthy young and elderly subjects. The numbers of Treg cells in peripheral blood, their influence on CD8+ T and NK cells and production of IL2 as well as apoptosis intensity of Treg cells were measured. The number of Treg cells was higher in both elderly groups than in respective young ones. Compared to healthy subjects, those with medical conditions were revealed to have higher numbers of Treg cells. In addition, the highest accumulation of Treg cells in non-healthy elderly could be a result of their resistance to undergo apoptosis. The frequency of Treg cells correlated inversely with the activity of autologous cytotoxic cells in PBMC and production of IL2 by autologous CD4+CD25- Th cells. Thus, these parameters were the most highly decreased in non-healthy subjects, notably in the elderly. However, these parameters improved in the cultures of pure sorted cells. The only subset capable of decreasing them to the levels noted in PBMC when added back was Treg cells, which proved the link between the number of Treg cells, cytotoxic activity and production of IL2. Concluding, we found that Treg accumulated as a result of ageing and/or medical conditions were capable of decreasing cytotoxic activity of CD8+ T and NK cells and production of IL2.
Trzonkowski
Piotr
P
Department of Histology and Immunology, Medical University of Gdańsk, Ul. Debinki 1, 80-211 Gdańsk, Poland. ptrzon@amg.gda.pl
Szmit
Ewa
E
Myśliwska
Jolanta
J
Myśliwski
Andrzej
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D017209:Apoptosis; D015704:CD4 Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2; D054353:Perforin; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase