Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies, T cell surface marker expression, and serum IL-2 receptor levels as biomarkers of age and health

Hallgren, Helen M.; Bergh, Nona; Rodysill, Kirk J.; O’Leary, James J.

doi:10.1016/0047-6374(88)90045-0

Cited by 63 publications

(19 citation statements)

References 14 publications

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“…The results presented here confirm earlier findings [19,20] that T cells from the healthy aged show severely im paired responses to PHA. This defect was not the result of age-related differences in dose optima or response kinet ics.…”

Section: Discussionsupporting

confidence: 82%

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Age-Related Changes in the Expression of IL-2 and High-Affinity IL-2-Binding Sites

Beckman²,

Bradley³

1993

Int Arch Allergy Immunol

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T cell responsiveness to in vitro stimulation is severely diminished in the aged. Recent studies would suggest that this may be due, at least in part, to a reduction in interleukin 2 (IL-2) secretion and high-affinity IL-2 receptor (HA-IL-2R) expression. In this report we confirm and extend these studies to show that the fall in IL-2 production is not due to reduced numbers of IL-2 mRNA producing T cells but rather to a decline in the relative amount of IL-2 mRNA expressed per cell. Although we found an age-related reduction in the number of high-affinity binding sites on phytohaemagglutinin-activated T cell blasts by ligand-binding studies, we did not observe alterations in the number of cells that expressed both chains of the HA-IL-2R by two-colour immunofluorescence using monoclonal antibodies specific for p55 (α) chain and p75 (β) chain. However, we did observe a substantial diminution in the number of activated T cells expressing p55 alone in the aged. Given that IL-2 upregulates p55 expression and is involved in the formation of HA-IL-2R, our results suggest that defective IL-2 expression is the primary lesion in age-related T cell senescence.

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Section: Discussionsupporting

confidence: 82%

“…In agreement with our previous results [16,19] and those of others [4,20], [3H|TdR incorporation was found to be significantly reduced in the aged (30-45% of young adult controls; p < 0.05) in both kinetic and dose-related parameters ( fig. 2).…”

Section: Age-associated Defect In Pha-induced Proliferationsupporting

confidence: 82%

Age-Related Changes in the Expression of IL-2 and High-Affinity IL-2-Binding Sites

Beckman²,

Bradley³

1993

Int Arch Allergy Immunol

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“…Only levels of serum IgA were increased, as variably reported in the literature. 3,10,18,24,43 Such polyclonal elevations may result from cumulative antigen exposure over time, increased mucosal exposure, or perturbations of B-cell activation. Deficits in cellmediated immunity, as evidenced by poor lymphocyte responses to mitogens, have been one of the more consistent abnormalities described in elderly persons, particularly with T-lymphocyte mitogens.…”

Section: Commentmentioning

confidence: 99%

Immune Function and Vaccine Responses in Healthy Advanced Elderly Patients

Carson¹,

Nichol²,

O'Brien

et al. 2000

Arch Intern Med

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“…Many factors have been shown to be involved in the decreased immune responses of the elderly, including decreased thymic function (Tosi et al 1982;Utsuyama et al 1997), changes in peripheral T lymphocyte subpopulations (Deviere et al 1985;Brohee, 1987) and decreased capacity of peripheral T lymphocytes to be stimulated (Murasko et al 1986;Hallgren et al 1988). Environmental factors, particularly nutritional deficit, have also been shown to be involved in the age-related immune deficit, especially in aged patients (Chandra, 1988;Lesourd, 1990b;Feldman, 1993).…”

Section: Immune Response: Disease: Ageing: Elderlymentioning

confidence: 99%

Immune response during disease and recovery in the elderly

Lesourd

1999

Proc. Nutr. Soc.

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The present article reviews immune ageing and its relationship with nutritional ageing, with a particular insight into the influences of disease on both ageing processes. Immune ageing can be described primarily as the progressive appearance of immune dysregulations, mainly acquired immunity (mature: immature, naive: memory T lymphocyte subset decreases) leading to gradual increases in T-helper 2: T-helper 1 cells. This change is due initially to decreased thymic function, and later to accumulative antigen pressure over the lifespan. In contrast, innate immunity (macrophage functions) is preserved during the ageing process and in the elderly this leads to macrophage-lymphocyte dysequilibrium, which is particularly critical during on-going disease. Indeed, any disease induces long-lasting acute-phase reactions in aged patients and leads to body nutritional reserve (mainly protein) losses. Episodes of disease in the aged patient progressively deplete body nutritional reserves and lead to proteinenergy malnutrition, undernutritionassociated immunodeficiency, and finally cachexia. Undernutrition is a common symptom in the elderly; proteinenergy malnutrition is found in more than 50 % of hospitalized elderly patients and in most elderly diseased subjects. In addition, micronutrient deficit or low levels are common in home-living self-sufficient apparently-healthy elderly subjects. All these nutritional deficits induce decreased immune responses, and micronutrient deficits are now thought to be partly responsible for the decreased immune responses (immune ageing?) observed in the apparentlyhealthy elderly. Indeed, several studies have shown that micronutrient supplements induce increased immune responses in the healthy elderly. The progression of infectious diseases depends on immune responses and on nutritional status before the onset of illness in aged subjects. In addition, recovery depends on the intensity of acute-phase responses in the undernourished elderly. In fact, chronic acute-phase responses, commonly associated with diseases in aged patients, lead to progressive lowering of metabolic responses in the undernourished elderly. This can be quantified by increased production of free radicals during treatment and these increases may explain the difficulty in successfully treating aged patients. Nutritive therapy in order to improve metabolic processes and also to maintain body reserves should be considered as a necessary adjuvant therapy in the treatment of elderly patients. Immune response: Disease: Ageing: ElderlyOne of the most important changes for man in the 20th century is a drastic increase in life expectancy. Life expectancy has almost doubled in the last 100 years (Haut ComitC de la SantC Publique, 1994). As a consequence, the elderly population is rapidly increasing. In France, the elderly population (>60 years) has grown from 10 9% in 1960 to 17 % in 1992, and will continue to increase to comprise onethird of the population by 2030 (Institut National de la Statistique et des Etudes Epidemiologiques, ...

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Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies, T cell surface marker expression, and serum IL-2 receptor levels as biomarkers of age and health

Cited by 63 publications

References 14 publications

Age-Related Changes in the Expression of IL-2 and High-Affinity IL-2-Binding Sites

Age-Related Changes in the Expression of IL-2 and High-Affinity IL-2-Binding Sites

Immune Function and Vaccine Responses in Healthy Advanced Elderly Patients

Immune response during disease and recovery in the elderly

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