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Is thymocyte development functional in the aged?

Aw D, Silva AB, Palmer DB - Aging (Albany NY) (2009)

Bottom Line: T cells are an integral part of a functional immune system with the majority being produced in the thymus.However, current data suggests that recent thymic emigrant from the aged thymus are functionally less responsive, giving rise to the possibility that the generation of naïve T cell may be intrinsically impaired in the elderly.In light of these findings we discuss the evidence that suggest aged T cells may be flawed even before exiting to the periphery and could contribute to the age-associated decline in immune function.

View Article: PubMed Central - PubMed

Affiliation: Infection & Immunity and Genes & Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, UK.

ABSTRACT
T cells are an integral part of a functional immune system with the majority being produced in the thymus. Of all the changes related to immunosenescence, regression of the thymus is considered one of the most universally recognised alterations. Despite the reduction of thymic size, there is evidence to suggest that T cell output is still present into old age, albeit much diminished; leading to the assumption that thymocyte development is normal. However, current data suggests that recent thymic emigrant from the aged thymus are functionally less responsive, giving rise to the possibility that the generation of naïve T cell may be intrinsically impaired in the elderly. In light of these findings we discuss the evidence that suggest aged T cells may be flawed even before exiting to the periphery and could contribute to the age-associated decline in immune function.

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Aged thymocytes have increased resistance to spontaneous and dexamethasone-induced apoptosis. Spontaneous (A) and                                            dexamethasone (dex)-induced (B) apoptosis at 0.5nM was assessed by                                            flow cytometry. Graphs show the percentage of viable thymocytes defined as                                            Annexin V- 7AAD- (top graphs)and                                            those undergoing early apoptosis as Annexin V+ 7AAD-                                            (bottom graphs). Closed square/circle with dotted line symbolise                                            young thymocytes cultured in media or with the addition of 0.5nM dex                                            respectively. Whereas, open square/circle with solid line signify                                            thymocytes from 18 month old mice cultured in media or with the addition of                                            0.5nM dex respectively. The data revealed that there is an                                            age-associated increased resistance to spontaneous and dex-induced                                            apoptosis with a higher percentage of viable thymocytes from older mice                                            compared to younger mice and delayed kinetic of older thymocytes to                                            initiate apoptosis. Data representative of four experiments. *P<0.05;                                            **P<0.01.
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Figure 4: Aged thymocytes have increased resistance to spontaneous and dexamethasone-induced apoptosis. Spontaneous (A) and dexamethasone (dex)-induced (B) apoptosis at 0.5nM was assessed by flow cytometry. Graphs show the percentage of viable thymocytes defined as Annexin V- 7AAD- (top graphs)and those undergoing early apoptosis as Annexin V+ 7AAD- (bottom graphs). Closed square/circle with dotted line symbolise young thymocytes cultured in media or with the addition of 0.5nM dex respectively. Whereas, open square/circle with solid line signify thymocytes from 18 month old mice cultured in media or with the addition of 0.5nM dex respectively. The data revealed that there is an age-associated increased resistance to spontaneous and dex-induced apoptosis with a higher percentage of viable thymocytes from older mice compared to younger mice and delayed kinetic of older thymocytes to initiate apoptosis. Data representative of four experiments. *P<0.05; **P<0.01.

Mentions: Aged peripheral T cells from either humans or mice demonstrate an increased resistance to apoptosis [43,44]. Although these cells may represent the most terminally differentiated T cells, suggesting that increased resistance to apoptosis is the outcome of senescence, a study investigating in vivo responses to activation induced cell death of T cells from aged mice implies age-related impairment of apoptosis can occur in previously unchallenged T cells and is perhaps intrinsically acquired [45]. In this study, male SCID mice receiving adoptively transferred T cells from old female HY TCR transgenic mice had a three-fold increase in the percentage of autoreactive CD8+ HY antigen-reactive T cells in contrast to mice receiving T cells from young female transgenic mice. Moreover, in our laboratory we have observed an age-dependent resistant to spontaneous and dexamethasone-induced apoptosis in murine thymocytes (Figure 4), which has also been reported in rat thymocytes [41]. Therefore, the resistance to apoptosis observed in thymocytes from older mice may be reflected in decreased susceptibility of peripheral T cells to undergo cell death.


Is thymocyte development functional in the aged?

Aw D, Silva AB, Palmer DB - Aging (Albany NY) (2009)

Aged thymocytes have increased resistance to spontaneous and dexamethasone-induced apoptosis. Spontaneous (A) and                                            dexamethasone (dex)-induced (B) apoptosis at 0.5nM was assessed by                                            flow cytometry. Graphs show the percentage of viable thymocytes defined as                                            Annexin V- 7AAD- (top graphs)and                                            those undergoing early apoptosis as Annexin V+ 7AAD-                                            (bottom graphs). Closed square/circle with dotted line symbolise                                            young thymocytes cultured in media or with the addition of 0.5nM dex                                            respectively. Whereas, open square/circle with solid line signify                                            thymocytes from 18 month old mice cultured in media or with the addition of                                            0.5nM dex respectively. The data revealed that there is an                                            age-associated increased resistance to spontaneous and dex-induced                                            apoptosis with a higher percentage of viable thymocytes from older mice                                            compared to younger mice and delayed kinetic of older thymocytes to                                            initiate apoptosis. Data representative of four experiments. *P<0.05;                                            **P<0.01.
© Copyright Policy - open-access
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Figure 4: Aged thymocytes have increased resistance to spontaneous and dexamethasone-induced apoptosis. Spontaneous (A) and dexamethasone (dex)-induced (B) apoptosis at 0.5nM was assessed by flow cytometry. Graphs show the percentage of viable thymocytes defined as Annexin V- 7AAD- (top graphs)and those undergoing early apoptosis as Annexin V+ 7AAD- (bottom graphs). Closed square/circle with dotted line symbolise young thymocytes cultured in media or with the addition of 0.5nM dex respectively. Whereas, open square/circle with solid line signify thymocytes from 18 month old mice cultured in media or with the addition of 0.5nM dex respectively. The data revealed that there is an age-associated increased resistance to spontaneous and dex-induced apoptosis with a higher percentage of viable thymocytes from older mice compared to younger mice and delayed kinetic of older thymocytes to initiate apoptosis. Data representative of four experiments. *P<0.05; **P<0.01.
Mentions: Aged peripheral T cells from either humans or mice demonstrate an increased resistance to apoptosis [43,44]. Although these cells may represent the most terminally differentiated T cells, suggesting that increased resistance to apoptosis is the outcome of senescence, a study investigating in vivo responses to activation induced cell death of T cells from aged mice implies age-related impairment of apoptosis can occur in previously unchallenged T cells and is perhaps intrinsically acquired [45]. In this study, male SCID mice receiving adoptively transferred T cells from old female HY TCR transgenic mice had a three-fold increase in the percentage of autoreactive CD8+ HY antigen-reactive T cells in contrast to mice receiving T cells from young female transgenic mice. Moreover, in our laboratory we have observed an age-dependent resistant to spontaneous and dexamethasone-induced apoptosis in murine thymocytes (Figure 4), which has also been reported in rat thymocytes [41]. Therefore, the resistance to apoptosis observed in thymocytes from older mice may be reflected in decreased susceptibility of peripheral T cells to undergo cell death.

Bottom Line: T cells are an integral part of a functional immune system with the majority being produced in the thymus.However, current data suggests that recent thymic emigrant from the aged thymus are functionally less responsive, giving rise to the possibility that the generation of naïve T cell may be intrinsically impaired in the elderly.In light of these findings we discuss the evidence that suggest aged T cells may be flawed even before exiting to the periphery and could contribute to the age-associated decline in immune function.

View Article: PubMed Central - PubMed

Affiliation: Infection & Immunity and Genes & Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, UK.

ABSTRACT
T cells are an integral part of a functional immune system with the majority being produced in the thymus. Of all the changes related to immunosenescence, regression of the thymus is considered one of the most universally recognised alterations. Despite the reduction of thymic size, there is evidence to suggest that T cell output is still present into old age, albeit much diminished; leading to the assumption that thymocyte development is normal. However, current data suggests that recent thymic emigrant from the aged thymus are functionally less responsive, giving rise to the possibility that the generation of naïve T cell may be intrinsically impaired in the elderly. In light of these findings we discuss the evidence that suggest aged T cells may be flawed even before exiting to the periphery and could contribute to the age-associated decline in immune function.

Show MeSH
Related in: MedlinePlus