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

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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.

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Acknowledgements

This work was supported by the Grant No. 175050 from the Ministry of Education, Science and Technological Development of the Republic of Serbia.

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11010_2017_2989_MOESM1_ESM.tif

Supplementary figure 1. Flow cytometry gating strategy for analyzing CD4+ and CD8+ T-cell subpopulations and T cells at distinct stages of activation/maturation. (Panel A) Flow cytometry dot plot indicates CD4 vs CD8 staining of TCRαβ+ PBLs gated as shown in the corresponding flow cytometry histogram. (Panel B) Flow cytometric analysis of TCRαβ+ PBLs isolated using magnetic-activated cell sorting (MACS). Dot plots indicate CD45RC vs CD90 staining of (upper subpanel) CD4+ and (lower subpanel) CD8+ TCRαβ+ PBLs, gated as shown in the corresponding flow cytometry histograms. Cells within the regions indicated in the dot plots correspond to (upper left) recent thymic emigrants (CD90+CD45RC- cells) (lower left) memory/activated cells (CD90-CD45RC- cells) and (right) mature naïve cells (CD45RC+ cells) (TIF 486 KB)

11010_2017_2989_MOESM2_ESM.tif

Supplementary figure 2. Flow cytometry gating strategy for analyzing CD25+Foxp3+ cells within CD4+ and CD161+ cells within CD8+ T cells. (Panel A) Flow cytometry dot plots indicate (right) CD25 vs Foxp3 staining of (left) gated CD4+TCRαβ+ PBLs. (Panel B) Flow cytometry dot plots indicate (right) CD161 staining of (left) gated CD8+TCRαβ+ PBLs (TIF 341 KB)

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Arsenović-Ranin, N., Kosec, D., Pilipović, I. et al. Sex and age as determinants of rat T-cell phenotypic characteristics: influence of peripubertal gonadectomy. Mol Cell Biochem 431, 169–185 (2017). https://doi.org/10.1007/s11010-017-2989-x

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