ABSTRACT
To define the effect of estrogen and progesterone concentrations achieved during hormonal contraceptive therapy (HCT) on cell-mediated immunity (CMI) of HIV-infected and uninfected subjects, peripheral blood mononuclear cells (PBMCs) from varicella-zoster virus (VZV)-seropositive individuals were treated with 0.1 ng/mL of estradiol, 33 ng/mL of norgestrel, and 13 ng/mL of dexamethasone and tested for VZV CMI. Estrogen and progesterone decreased VZV lymphocyte proliferation and T helper (Th) 1/inflammatory cytokine secretion, albeit less than dexamethasone. Progesterone decreased the expression of CD69 activation marker on CD8 and CD14 cells and increased the expression of Fas ligand (CD178) on CD14 monocytes, suggesting that induction of apoptosis may contribute to the inhibitory effect of this hormone. Cytokine production of separated CD4, CD8, and CD14 cells confirmed the effect of progesterone on all 3 cellular types, whereas the effect of estrogen was restricted to CD14 monocytes. The estrogen- and progesterone-mediated inhibition of Th1/inflammatory cytokines was greater in HIV-infected subjects (35% decrease for both hormones) compared with uninfected subjects (12% and 19% for estrogen and progesterone, respectively), whereas the effect on proliferation and PBMC phenotype did not differ by HIV status. Overall, HCT concentrations of estrogen and progesterone downregulated ex vivo VZV CMI of HIV-infected and uninfected subjects.
Subject(s)
Dexamethasone/pharmacology , Estradiol/pharmacology , HIV Infections/immunology , Immunity, Cellular/drug effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Norgestrel/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Cytokines/metabolism , Female , Herpesvirus 3, Human/immunology , Humans , Leukocytes, Mononuclear/virologyABSTRACT
The enigmatic fern genus Diellia, endemic to the Hawaiian archipelago, consists of five extant and one recently extinct species. Diellia is morphologically highly variable, and a unique combination of characters has led to several contrasting hypotheses regarding the relationship of Diellia to other ferns. A phylogenetic analysis of four chloroplast loci places Diellia within 'black-stemmed' rock spleenworts of the species-rich genus Asplenium, as previously suggested by W. H. Wagner. Using an external calibration point, we estimate the divergence of the Diellia lineage from its nearest relatives to have occurred at ca. 24.3 Myr ago matching an independent estimate for the renewal of Hawaiian terrestrial life (ca. 23 Myr ago). We therefore suggest that the ancestor of the Diellia lineage may have been among the first successful colonists of the newly emerging islands in the archipelago. Disparity between morphological and nucleotide sequence variation within Diellia is consistent with a recent rapid radiation. Our estimated time of the Diellia radiation (ca. 2 Myr ago) is younger than the oldest island of Kaua'i (ca. 5.1 Myr ago) but older than the younger major islands of Maui (ca. 1.3 Myr ago), Lana'i (ca. 1.3 Myr ago) and Hawaii (ca. 0.43 Myr ago).
