Progressive polarization towards a T helper/cytotoxic type-1 cytokine pattern during age-dependent maturation of the immune response inversely correlates with CD30 cell expression and serum concentration

Abstract

SUMMARYIn order to investigate the T cell cytokine profile during age-dependent maturation of the immune response, we evaluated the cytokine expression of CD4 þ and CD8 þ circulating cells by flow cytometric single-cell analysis after non-specific stimulation in vitro in different age groups of normal individuals, from cord blood to adulthood. Moreover, we correlated these lymphocyte cytokine patterns with the expression/release of CD30, a member of the tumour necrosis factor (TNF) receptor superfamily, which has been suggested to be related to the T helper/cytotoxic (Th(c))2-type immune responses, in order to verify this association in vivo, in non-pathological conditions. The results showed a progressive increase of circulating Th(c)1-type, interferon-gamma (IFN-g)-and/or IL-2-producing T cells along with ageing and, conversely, a stable number, although higher than in cord blood samples, of CD4 þ /IL-4 þ T cells in the post-natal groups. In addition, serum levels of soluble CD30 (sCD30) and numbers of circulating CD4 þ /CD30 þ and CD8 þ /CD30 þ T cells were significantly higher in children aged < 5 years in comparison with those found either in cord blood or in blood from both older children and adults. These data support the concept of a progressive polarization of the Th(c) cell cytokine profile towards the Th(c)1 pattern during age-dependent maturation of the immune response. Moreover, the peak of CD30 expression/release in early infancy before the Th(c)1 shifting occurs, although not associated with a significant increase of circulating IL-4 þ T cells, raises the question of the possible relationship in vivo between CD30 and Th(c)2-type immune responses.

Defective antigen-presenting cell function in human neonates

“…Interestingly, neonates appear to exhibit a predisposition toward production of Th2 cytokines after exposure to environmental allergens [85,2], followed by an age-dependent change toward Th-1-like responses [86,87]. This Th2 bias is usually considered to be a major underlying mechanism for the development of atopy in early life, and could again be a consequence of APC defects.…”

Lymphocyte Modulation in a Baboon Model of Immunosenescence

“…Therefore, the finding of a sharp age-related decline in levels of IL-2R␣ in serum in conjunction with very low, stable levels of cell surface expression of CD25 indicates that T-cell function is regulated through different mechanisms at different ages in baboons. Because of the decline of IL-2R␣ in serum, we tested all animals for an increase in levels of sCD30 in serum: sCD30 is a marker indicating the anti-inflammatory activity of Th0/Th2 lymphocytes (20) and is known to be present at higher levels in healthy centenarians (14). There was no effect of age on sCD30 levels, thus suggesting lack of a major increase in Th0/Th2 activity in older baboons.…”

Serum Levels of Soluble CD26 and CD30 in Patients on Hemodialysis

“…Another study has demonstrated that the serum level of sCD30 and the circulating CD30 expression in helper T cells were significantly higher in young children than in elder children and adults. This indicates that helper T cells may induce the production of more cells subjected to Th1 in older than younger people [41]. In our study, the serum level of sCD26 was not significantly correlated with age, while the serum level of sCD30 showed a significant inverse correlation with age in patients on HD.…”