CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly

Abstract

Age-related declines in immune function have an impact on both primary and memory responses. In this study, we have examined the ability of naive CD4 T cells from young and aged T cell receptor transgenic mice to establish functional memory. We found that memory cells generated from young CD4 T cells responded well to antigen, even a year after generation, whereas memory cells derived from CD4 T cells from aged mice responded poorly both ex vivo and in vivo. Memory cells generated from aged naive cells proliferate less, produce reduced levels of cytokines, and exhibit reduced cognate helper function, compared with memory cells generated by using young naive cells. These results indicate that it is the age of the naive T cell when it first encounters antigen, rather than the age when it reencounters antigen, that is critical for good memory CD4 T cell function.

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

“…Such individuals also have higher levels of memory and effector T cells, 46 yet are in general hypo-responsive and referred to as immunosenescent. [47][48][49][50] Other than the higher frequency of memory and activated T cells in aged CD300f-deficient mice and the presence of elevated ANA, the T-cell proliferation in response to TCR stimulation, the activation status of macrophages or DC based on co-stimulatory molecule expression, and the levels of inflammatory or anti-inflammatory cytokines were similar between CD300f-deficient and WT mice, suggesting an immunosenescent status in aged mice. Thus, our data indicate that the autoimmune-risk status generated by CD300f deficiency occurs in the context of immunosenescence, which explains the absence of overt disease pathologies.…”

The effect of aging on cognate function and development of immune memory

“…It is also important to note that, in older animals that were primed during youth, antigenspecific CD4 + and CD8 + memory T cells respond well, whereas the naïve T cells in these aged animals have significant defects in primary responses [3,4]. These observations suggest that age-related defects that negatively influence the primary response of naïve T cells do not have the same detrimental effects on memory cells.…”

“…As individuals age, the peripheral immune system becomes dominated by memory lymphocytes [2], but it has been unclear if these cells are functional and able to confer significant protection from infection. Recent studies suggest that immunological memory generated during youth functions well into old age, whereas that generated later in life does not function well at all [3,4]. This point is important, as the elderly are increasingly targeted for vaccinations for infectious diseases, such as influenza and pneumococcal pneumonia, even though these vaccines have significantly decreased efficacy in older individuals [5,6].…”

Aging, imbalanced inflammation and viral infection

“…In addition, aging leads to defective CD4 + and CD8 + memory T cell function. 18,19 Other components of the adaptive immune system, including antibody formation by B cells, may also be altered with aging. 20,21 Less is known about the role of aging in innate immunity, which is the first line of host defense against infections.…”