Resting Regulatory T Lymphocytes: A Biomarker for Chronic GVHD
Year: 2012
Type: article
Study design: Observational Study
Abstract: T cell depletion and peri-transplant serotherapy have reduced the incidence and severity of acute graft versus host disease (GVHD); however, chronic GVHD continues to be a major clinical limitation to the increased use of hematopoietic stem cell transplantation (HSCT). Deficiencies in naturally occurring regulatory T lymphocytes (Treg) have been hypothesized to contribute to chronic GVHD. The evaluation of the role of Treg lymphocytes in the pathogenesis of chronic GVHD have been limited by a lack of well-defined immunophenotypic characterization of Treg lymphocytes. Most previous evaluations of Treg lymphocytes in HSCT recipients, which used either CD25 and/or FoxP3 expression, were confounded by the fact that activated conventional T lymphocytes (Tcon) expressed CD25 and FoxP3. We have performed a cross-sectional analysis of pediatric HSCT recipients using the Miyara classification of Treg lymphocytes. (Immunity 30:899, 2009) The Miyara classification can distinguishes between Treg lymphocytes, both resting and activated, and activated Tcon lymphocytes, permitting a more accurate assessment of Treg in the HSCT setting. Pediatric HSCT recipients more than 1 year post-HSCT were evaluated for their resting (r) and activated (a) Treg lymphocytes and their r/a ratio determined. (Table 1)Table 1Resting and Activated Treg Lymphocytes in HSCT RecipientsPatientrTregaTregr/a ratio(% of total CD4 T lymphocytes x 10−1)Allogeneic-No hx of acute/chronic GVHD17.36.24.7Active chronic GVHD6.41.83.5Hx of chronic GVHD14.06.83.2Autologous11.35.22.2Normal Individuals19.33.63.9 Open table in a new tab Allogeneic HSCT recipients with no history of either acute or chronic GVHD did not differ from normal individuals. Neither did allogeneic recipients with only a history of acute GVHD nor the recipients of autologous HSCT. Allogeneic recipients with active chronic GVHD had reductions in both the percentage of resting Treg lymphocytes (p = .02 compared to normal or recipients with neither acute nor chronic GVHD) and of activated Treg lymphocytes (p = .002 compared to recipients without acute or chronic GVHD and p = .0008 compared to normals). Allogeneic recipients, who have had the clinical resolution of their chronic GVHD, did not differ from normal individuals. The clinical resolution of chronic GVHD is associated with a normalization of both resting and activated Treg lymphocytes. The longitudinal evaluation of resting Treg levels may aid in the management of chronic GVHD patients and may predict when clinical improvement occurs.
Institution: Children's Hospital Los Angeles
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W1994013823