(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email email@example.com.
Conditional ablation of LYVE-1+ cells unveils defensive roles of lymphatic vessel in intestine and lymph nodes, Jang et al.
Lymphatic vessels have traditionally been thought of as passive drainage vessels that transport excess fluid back into the blood; however, recent studies suggest that they may have other important physiologic roles. In this week’s issue of Blood, Jang and colleagues demonstrate a critical role for lymphatics in maintaining gut integrity, detailing the results of an experiment involving a transgenic mouse model in which investigators successfully expressed diphtheria toxin in lymphatic endothelial cells to ablate lymphatic vessels. The mice died unexpectedly of septic shock within 24 to 60 hours, and investigators observed loss of lymphatic lacteals in intestinal villi, with distortion of the villous architecture and vasculature and translocation of intestinal flora into the blood. This observation demonstrates a previously undescribed role for lymphatic vessels in maintaining the integrity of the intestine and protecting against sepsis.
HIV-1 Infection of hematopoietic progenitor cells in vivo in humanized mice, Nixon et al.
While the earliest observations of HIV infection included recognition of associated hematologic abnormalities, the exact pathogenesis of cytopenias has been unclear. In this week’s issue of Blood, Nixon and colleagues utilize a humanized mouse model to elucidate some of the intensely debated hypotheses for the origin of cytopenias, including whether HIV can directly infect CD34+ cells and whether the infected cells can serve as a reservoir of HIV infection. In the manuscript, investigators report that CD34+CD38+ hematopoietic progenitors express HIV-1 entry receptors and can indeed be infected by HIV, and infected cells develop impaired hematopoietic differentiation leading to progeny harboring provirus. Infection was cytotoxic in some cells; however, others were permissive of infection and survived despite harboring proviral DNA. Although this report does not definitively resolve the controversy, it strongly suggests that HIV can infect hematopoietic progenitors and also provides an excellent model in which to study these issues further.
Human regulatory T cells against minor histocompatibility antigens: ex vivo expansion for prevention of graft-versus-host disease, Veerapathran et al.
Graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical donors is thought to be caused by alloreactive T cells directed against unmatched minor histocompatibility antigens (mHA). In this week’s issue of Blood, Veerapathran and colleagues explore isolation and expansion of regulatory T cells (Tregs) as a potential technique to block GVHD. In their manuscript, investigators demonstrate that CD4 T-cell responses to specific antigens can be suppressed by purifying Tregs from normal donors and stimulating them with dendritic cells from HLA-matched siblings. They also isolated mHA-specific Tregs from blood samples and expanded them in vitro. These encouraging studies lay the groundwork for future clinical trials using mHA-specific Tregs to block GVHD.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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