Influence of oxygen concentration on T cell proliferation and susceptibility to apoptosis in healthy men and women

Abstract

Introduction.Much of what we know about the functioning of human T lymphocytes is based on the experiments carried out at atmospheric oxygen (O 2 ) concentrations, which are significantly higher than those maintained in blood. Interestingly, the gender differences in the activity of T cells and their susceptibility to apoptosis under different O 2 conditions have not yet been described. The aim of the study was to compare two main markers of lymphocyte function: proliferation capacity and ability to produce cytokines as well as their susceptibility to apoptosis under two different O 2 concentrations, between men and women. Material and methods. 25 healthy volunteers, both males (13) and females (12) were recruited to the study (mean age 25.48 ± 5.51). By using cytometry proliferation parameters of human CD4 + CD28+ cells or CD8 + CD28 + cells in response to polyclonal stimulation of the TCR/CD3 complex at atmospheric (21%) and physiological (10%) O 2 concentrations using our modified dividing cell tracking technique (DCT) were analyzed as well as the percentages of apoptotic cells. We also determined the levels of IFN-g, IL-2, IL-10 and IL-17A using Cytometric Bead Array Flex system in cell culture supernatants. Results. CD4+ CD28 + and CD8 + CD28 + cells from the whole study group were characterized by shorter time required to enter the first (G1) phase of the first cell cycle at 21% compared to 10% O 2 . Both T cell populations performed significantly more divisions at 21% O 2 . The percentages of dividing cells were also significantly higher at atmospheric O 2 . Interestingly, data analysis by gender showed that male lymphocytes had similar proliferative parameters at both O 2 concentrations while female lymphocytes proliferate more efficiently at 21% oxygen. Compared to males, the female CD4 + cells showed increased susceptibility to apoptosis at both O 2 concentrations. No differences in the levels of cytokines regardless of gender and oxygen conditions were found. Conclusions. We showed that in vitro female T cells (both CD4 + and CD8 + cells) are more sensitive than male lymphocytes to low O 2 concentration as demonstrated by the decrease in their proliferation dynamics. The effect does not depend on increased apoptosis of female T cells under low O 2 because percentage of apoptotic cells was similar at both O

Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of rat collagen-induced arthritis

“…This may be linked with estrogen-sensitive PPARγ/dependent differentiation of Tfh cells 59 . A more prominent increase in the number of Tfh cells in female rat dLNs following immunization with CII leading to sex bias in their number in immunized rats (greater number in females) was consistent with data indicating that Th cells from adult women and female mice have greater proliferative capacity than those from age-matched men and male mice, respectively 60,61 . Additionally, we have recently shown the greater activation/proliferation of Th cells from dLNs of female CII-immunized DA rats compared with their male counterparts 10 .…”

Nocturnal oxygen therapy as an option for early COVID-19

“…A recent study revealed that breathing 60% O 2 increased activities of T and NK cells, and decreased immunosuppressive molecules in a murine lung cancer model (Hatfield et al, 2015). Some researchers have also demonstrated that lymphocytes have higher proliferation efficiency in conditions of rich O 2 compared with hypoxia (Waskowska et al, 2017;Atkuri et al, 2005b). Accordingly, it is tempting to speculate that sufficient O 2 may improve the antiviral ability of patients with early COVID-19 by increasing the abundance and activities of immune cells.…”