Lymphocyte Modulation in a Baboon Model of Immunosenescence

Abstract

The age-related modulation of lymphocyte number and function was assessed in a nonhuman primate model consisting of healthy olive baboons (Papio cynocephalus anubis) of ages encompassing the entire life span of this species. The objectives of this study were to characterize an animal model of immunosenescence and to assess whether or not age should be considered when designing studies for the evaluation of vaccine candidates in baboons. Specifically the following parameters were assessed in baboons from 6 months to 26 years of age: relative numbers of B lymphocytes, CD4؉ and CD8 ؉ T lymphocytes, and T lymphocytes expressing CD28, CD25, and phytohemagglutinin-stimulated lymphoproliferative activity; and concentrations of total immunoglobulin, soluble interleukin-2 receptor ␣, and soluble CD30 in serum. There was a statistically significant effect of age on lymphocyte numbers. As age increased, relative B-cell numbers (ranging from 6 to 50%) decreased (P < 0.001) and relative T-cell numbers (ranging from 28 to 80%) increased (P < 0.001). The increase in T-cell numbers involved both the CD4 ؉ and CD8 ؉ subsets. In addition, there was a significant negative correlation of age with levels of soluble interleukin-2 receptor ␣ in serum. Modulation of lymphocyte numbers appears to occur gradually during the entire baboon life span, thus suggesting the presence of an age-related developmentally regulated process. These findings indicate that baboons represent a potentially useful model to study selected phenomena related to immunosenescence. These findings also indicate that, when using the baboon model for vaccine or other experimental protocols requiring the assessment of immune responses, it would be appropriate to take into account the age of the animals in the study design.The immune system undergoes several functional changes during the aging process. These changes are thought to lead to an age-related increase in susceptibility to infectious diseases, autoimmune disorders, and cancer (26). Both humoral and cellular immune responses are subjected to age-related alterations, including decreased T-and B-cell responses to foreign antigens and increased responses to self-antigens (1,26,28,40). Decreased responses to foreign antigens are associated with the increased morbidity and mortality from infectious diseases as well as with the low vaccine efficacy observed in individuals over 65 years of age (41). The most striking evidence of the changing T-cell compartment is provided by thymic involution, which leads to decreased production of naive T lymphocytes and therefore to limited diversity of the T-cell receptor, although thymic output is present at high levels in elderly individuals (1). The dysregulated humoral immunity is characterized by decreased production of antibodies to most foreign antigens and increased production of autoantibodies. Indeed, there is a shift in number and activity of B lymphocytes, from B2 to B1 lymphocytes (19), that produce polyreactive autoantibodies encoded by variable region genes in a g...

Aging mechanism as the “down side” of adaptation: A network approach

“…Initially, we observe a rapid adaptation/optimization followed by a steady state with increasing rigidity -and an eventual final break down of the system. Interestingly, these theoretical predictions largely mimic the dynamics of recent data on the activity of the adaptive immune system during aging in Baboon monkeys (Jayashankar et al, 2003). Though simplistic, the model thus captures a generic property of aging in biological systems.…”

“…A marker for overall T-cell activation is the serum concentration of the surface receptor IL-2Rα (Morris & Waldmann, 2000) and in Figure 4, the serum level of IL-2Rα is plotted as a function of age in Olive Baboon monkeys (data from Jayashankar et al (2003)). As can be seen in the figure, in the beginning of the Baboon's life the level of T-cell activation is high but rapidly decreases within the first 50 months (∼ 4 years) of the baboon's lifetime.…”

“…4. Data obtained by Jayashankar et al (2003) showing the relationship between levels of the surface receptor IL-2Rα in serum and age in Olive Baboon monkeys. IL-2Rα is determined by ELISA and expressed in picograms per milliliter.…”

“…As can be seen from the plot, a linear fit is not appropriate, whereas the dynamics seen in our model is closer to the actual dynamics observed in this biological sub-system during senescence (see Figure 3). (Figure modified from (Jayashankar et al, 2003).…”

Comparative Pathology of Aging Great Apes

“…126 Examination of causes of mortality in captive ape populations subjectively showed no increase in infections with advanced age. 85,155,170 Infections were common among all age classes of free-ranging mountain gorillas and chimpanzees that we reviewed (L.J.L., K.A.T.).…”