Immunosenescence, Aging, and Systemic Lupus Erythematous
Table 1
Age-associated changes in immune cell populations and functions.
Cell type
Characteristics
References
Innate immunity
Neutrophils
↓ Phagocytic chemotaxis capability ↓ Superoxide anion production ↓ Ability to respond to soluble factors (GM-CSF) and bacteria (LPS and fMLP) ↓ Molecule recruitment into lipid raft, apoptosis, and signal transduction
↓ Cell number, antigen presentation, TLR-mediated signaling, IFN I/III production, chemotaxis, and endocytosis ↓ Ability to stimulate lymphocytes in the ill elderly ↑ Function in the healthy elderly
↓ Phagocytic activity and chemotaxis ↑ Synthesis of proinflammatory cytokines (IL-6, IL-8, TNF-, and IL-1β) ↓ Apoptosis, superoxide production, and signal transduction ↓ TLR expression and function ↑ PGE2 production ↓ MCH class II production
↑ CD56dimCD57+ population ↓ Function of cytotoxicity ↓ Secretion of IFN-γ induced by Interleukin 2 (IL-2) ↓ HLA-DR, IFN-α, CD57, and CD95 ↓ Cell proliferation ↑ Production of IL-1, IL-4, IL-6, IL-8, and TNF-α
Variable number (↓ proliferation to PHA, varying age, and health status)—HLA B8/DR3 associated with high proliferative responses ↑ Proportion of memory cells (CD45RO+), especially tissue CD8+ ↓ Proportion of naïve cells (CD45RA+) ↓ Proliferative capacity ↓ Synthesis of IL-2 receptor and IL-2 in memory cells ↓ CD28+ ↑ CD28− T cells—mainly CD8+ CD28− (characterized by oligoclonal expansion, shortening of telomeres, potentially decreased proliferation, resistance to apoptosis, and increased production of TNF-α and IL-6) ↓ CD4 T lymphocytes Change from Th1 response to Th2 response with ↓ cell-mediated responses directed against intracellular bacteria (Th1 function) and relative preservation of humoral response (Th2 function) ↓ Treg population (CD4+ CD25+) that plays a role in the manifestations of autoimmunity Impaired immunological synapse formation and signaling pathways (calcium response and phosphorylations) ↓ CD4/CD8 rate
↓ Pre-B lymphocytes with peripheral B lymphocyte count unchanged ↑ CD5+ B cells (CD19+ CD5+ clones B) that produce low affinity antibodies without cooperation of T cell ↓ Naïve B cells Accumulation of memory B cells with ↓ diversity and affinity of antibodies Reaching primary humoral response (dependent T cell cooperation). Conserved secondary humoral response
↑ Serum levels of IgA and IgG (IgG1, IgG2, and IgG4). Monoclonal immunoglobulin production by CD19+ CD5+ clones. Secretion of non-organ-specific self-antibodies (rheumatoid factor, antinuclear antibodies, antiphospholipid antithyroglobulines, and parietal cells).
↓ IL-2 production because of the following: ↓ cooperation of T cells with antibody producer B cells, ↑ production of IL-4, IL-6, IL-8, IL-10, and TNF-α, ↓ production of IL-1 and IFN-γ.
