Age-related autoantibody production in a nonhuman primate model

Attanasio, Roberta; Brasky, Kathleen M.; Robbins, Scott H.; Jayashankar, Lakshmi; Nash, Rodney J.; Butler, Thomas M.

doi:10.1046/j.1365-2249.2001.01454.x

Cited by 29 publications

(20 citation statements)

References 21 publications

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“…2) precludes the possibility that we detected ''background'' antibody levels of minor immunological importance. The age-associated increase in python antibody titres mirror results obtained in the studies of NAbs conducted on chicken (Parmentier et al 2004), mice (Bovbjerg et al 1991;Nobrega et al 1996), baboons (Attansio et al 2001) andhumans (Hallgren et al 1973;Candore et al 1997), strongly supporting that the age-associated increase in antibody titres in pythons reflect increasing levels of NAbs. The age-associated increase in NAbs have been suggested to reflect the polyclonal activation of B cells and the increase in spleen CD5+ B cells producing immunoglobulins (Benner et al 1981;LeMaoult et al 1997).…”

Section: Discussionsupporting

confidence: 65%

Do “infectious” prey select for high levels of natural antibodies in tropical pythons?

et al. 2006

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Natural antibodies (NAbs) constitute an important component in vertebrate immune system, but, in spite of this, have often been dismissed as ''non-specific background'' signals. We observed a significant positive relationship between water python (Liasis fuscus) body length/age and levels of antibodies reactive with two administered antigens (tetanus and diphtheria). However, no humoral immune response to the antigens was observed. The lack of elevated immune response, and the age-associated increase in antibody titres, strongly suggest that the antibodies consisted of polyreactive NAbs, and that absence of an elevated immune response was caused by such high levels of NAbs that they were able to mask the epitopes of the antigens. In our study area pythons feed mainly on rodents that frequently, before being killed, are able to inflict numerous bites to the snakes. The bites most likely transmit pathogens such as bacteria. As NAbs have been shown to act as a first line defence against bacterial infections, the high levels of NAbs in the pythons may be an adaptation to reduce pathogenic effects of bacteria transmitted by the prey when the snakes are feeding. Thus, the results from present study suggest that NAbs may have an important immunological function by reducing deleterious effects of pathogens in wild populations.

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Section: Discussionsupporting

confidence: 65%

Do “infectious” prey select for high levels of natural antibodies in tropical pythons?

et al. 2006

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“…In addition, major immunological similarities exist between humans and baboons. We have shown that baboons exhibit agerelated autoantibody production similar to that described in humans (2) and that baboon variable and constant region antibody genes are remarkably similar to their human counterparts (3,35). Here, we report that lymphocyte populations are modulated in older baboons.…”

Section: Discussionmentioning

confidence: 52%

Lymphocyte Modulation in a Baboon Model of Immunosenescence

Jayashankar¹,

Brasky

Ward

et al. 2003

Clin Vaccine Immunol

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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...

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“…the production of natural antibodies (henceforth NAbs; Nobrega et al. 1996; Attansio et al. 2001; Parmentier et al.…”

Section: Introductionmentioning

confidence: 99%

Do natural antibodies compensate for humoral immunosenescence in tropical pythons?

Újvári

Madsen

2011

Functional Ecology

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Summary 1.Ageing is frequently claimed to result in an age-dependent deterioration in immune function. 2. Our results, however, based on 30 known-aged water pythons (Liasis fuscus; age ranging from <1 to 18 years) immunized with keyhole limpet haemocyanin (KLH), demonstrate that agerelated changes in immune function may follow different and opposing pathways. 3. Python-specific humoral antibodies (SpAb) showed an age-dependent decrease in cross-reactivity to KLH, whereas natural antibodies (NAbs) ability to bind to this antigen increased with age. 4. Notably, when humoral SpAb and NAb titres were combined, no effect of age was detected in antibody cross-reactivity, strongly suggesting that NAbs may play a crucial role in maintaining immunocompetence during the ageing process.

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Age-related autoantibody production in a nonhuman primate model

Cited by 29 publications

References 21 publications

Do “infectious” prey select for high levels of natural antibodies in tropical pythons?

Do “infectious” prey select for high levels of natural antibodies in tropical pythons?

Lymphocyte Modulation in a Baboon Model of Immunosenescence

Do natural antibodies compensate for humoral immunosenescence in tropical pythons?

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