Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy

Abstract

The study examined the influence of age, sex and peripubertal gonadectomy on a set of T-cell phenotypic parameters. Rats of both sexes were gonadectomised at the age of 1 month and peripheral blood and spleen T lymphocytes from non-gonadectomised and gonadectomised 3- and 11-month-old rats were examined for the expression of differentiation/activation (CD90/CD45RC) and immunoregulatory markers. Peripheral blood T lymphocytes from non-gonadectomised rats showed age-dependent sexual dimorphisms in (1) total count (lower in female than male 11-month-old rats); (2) CD4+:CD8 + cell ratio (higher in female than male rats of both ages); (3) the proportion of recent thymic emigrants in CD8 + T cells (lower in female than male 3-month-old rats) and (4) the proportions of mature naïve and memory/activated cells (irrespective of age, the proportion of naïve cells was higher, whereas that of memory/activated cells was lower in females). Gonadectomy influenced magnitudes or direction of these sex differences. Additionally, sex differences in peripheral blood T-lymphocyte parameters did not fully correspond to those observed in T-splenocyte parameters, suggesting the compartment-specific regulation of the major T-cell subpopulations' and their subsets' composition. Furthermore, there was no sexual dimorphism in the proportion of either CD25 + Foxp3 + cells among CD4 + or CD161+ (NKT) cells within CD8 + T lymphocytes. However, there was gonadal hormone-independent age-associated sexual dimorphism in the proportion of CD161 + cells (NKT cells) in CD8 + T splenocytes. Overall, the study revealed age-dependent variations in sexual dimorphisms in T-cell parameters relevant for immune response efficacy and showed that they are T-cell compartment-specific and partly gonadal hormone-related.

Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases

“…Consistently, we showed that circulating levels of sex steroids in the critical early postnatal developmental "window" influence the kinetics of rat thymic involution, and contribute to sexual dimorphism in thymic size and function in old age [49][50][51][52]. Besides, we found that gonadectomy during peripubertal development leads to the reprogramming of kinetics of thymic involution [52][53][54][55] underlying molecular mechanisms have not yet been fully elucidated, an accumulating body of evidence suggests that these long-lasting effects of gonadal steroids on the size of rat thymus and thymopoiesis could be partly ascribed to their effects on reprogramming of thymic "(nor) adrenergic" regulatory cell networks [49][50][51][52][56][57][58].…”

Sexual Dimorphism of Immune Responses: A New Perspective in Cancer Immunotherapy

“…Conversely, high levels of estrogens, found in the follicular phase and during pregnancy, sustain Th2-mediated immunity characterized by IRF-1-mediated reduction of IFN-γ, IL-4 induction, and PD-1-overexpressing Tregs associated with reduced Th17 response ( 67 ). Nevertheless, estrogen together with other factors may directly stimulate Th17 cells inducing IL-17 production ( 68 ). Thus, females exhibit activated and proliferating CD4+ and CD8+ T cells, characterized by preferential production of IFNγ and high-cytotoxicity activity, whereas males exhibit IL-17-producing T cells ( 69 ).…”

Exploration of immune-related cells and ceRNA in squamous cell lung cancer

“…[ 10 ] In addition, CD4+ T cells were found to correspond to sex and age in mice. [ 11 ] Our findings revealed that there was a higher proportion of memory-activated CD4+ T cells in younger women. This finding may provide a suitable population for CD4 + T cell-related immunotherapy for SqCLC.…”