Differential Effects of Sex Steroids on T and B Cells: Modulation of Cell Cycle Phase Distribution, Apoptosis and bcl-2 Protein Levels

Abstract

Sex steroids have dramatic and differential effects on classic endocrine organ proliferation and apoptosis. In this investigation we sought to delineate similar effects of sex steroids on proliferation, cell cycle phase and apoptosis in lymphocyte cell lines as models for T and B cells. Estrogen and testosterone inhibited T cell line proliferation, induced accumulation of cells in S/G₂M phases of the cell cycle, and increased apoptosis in a concentration- and time-dependent manner. There was a more modest effect of estrogen and testosterone on cell cycling and apoptosis in B lymphocyte cell lines, suggesting that estrogen and testosterone are inhibitory to T but not B cell lines. In comparison, progesterone induced cytostasis and modestly increased apoptosis in both T and B cell lines. Estrogen and testosterone were not antagonistic or synergistic to each other in their effects on cell cycle phase distribution, and only minimally synergistic for apoptosis. In contrast, progesterone antagonized cell cycle and apoptotic effects of estrogen in T cells. Estrogen-induced cell cycle and apoptotic effects in T cell lines were associated with suppression of bcl-2 protein levels, which were unaffected in Raji B cells. Progesterone also antagonized the estrogen-induced changes in T cell bcl-2 protein levels. These results suggest that there may be significant and differential sex steroid effects on T and B lymphocytes that may be important to sexual dichotomies in immune and autoimmune responses.

Cyclical variation of leucocyte profile in healthy females: a comparison with males

“…The decreased lymphocyte counts in males as compared to females may be due to the increased testosterone concentrations, since testosterone may increase apoptosis in T cells 24 . Also studies in animals have shown an effect of estrogens on B cell development: estrogens increase bone marrow progenitor B cells in mice by protecting the progenitor cells from apoptosis 25 .…”

Effects of Xenoestrogens on T Lymphocytes: Modulation of bcl-2, p53, and Apoptosis

“…Cell cycle analysis was performed as previously described [38,39]. Briefly, 1×10 6 were grown in suspension, harvested by centrifugation, washed, and fixed in 1% paraformaldehyde.…”

“…For Western analysis, 2 to 5×10 6 cells were cultured (1.0×10 6 /ml) and stimulated bcl-2 and p53 protein levels were assayed as previously described [38,39]. All antibodies were diluted in 1 % milk in TBS.…”

“…As a result, ecohormones have the potential to variably modulate lymphocyte proliferation, cell cycle progression, apoptosis and cytokine production in much the same way as 17-β-estradiol does [36][37][38][39][40]. This modulation is likely to occur in association with alterations in T lymphocyte bcl-2 or p53 protein levels [28,29,38,39]. In this investigation, using the CD4+ Jurkat T lymphocyte cell line as a model [38][39][40], xenoestrogen-specific effects on T lymphocyte biology were initiated.…”

“…This modulation is likely to occur in association with alterations in T lymphocyte bcl-2 or p53 protein levels [28,29,38,39]. In this investigation, using the CD4+ Jurkat T lymphocyte cell line as a model [38][39][40], xenoestrogen-specific effects on T lymphocyte biology were initiated.…”