α1Antitrypsin Therapy Increases CD4+ Lymphocytes to Normal Values in HIV-1 Patients
Pp. 102-110 (9)
Cynthia L. Bristow, Jose Cortes, Roya Mukhtarzad, Maylis Trucy, Aaron Franklin, Val Romberg and Ronald Winston
Adult thymopoiesis is a multi-step process that in adult mice is highlighted by a 21-day cycle of
coordinated journeying of progenitor cells between adult bone marrow and thymus. In the analogous
human system, cell surface human leukocyte elastase (HLECS), the chemokine receptor CXCR4, and its
ligand stromal-derived factor-1 (SDF-1, CXCL12) are required for progenitor cells to vacate bone
marrow. We have recently observed that the number of circulating CD4+ lymphocytes is correlated with
the HLECS ligand, α1antitrypsin (α1proteinase inhibitor, α1PI). In HIV-1 disease, α1PI levels are deficient
and rate limiting for CD4+ lymphocytes. We demonstrate herein that α1PI therapy increases the number of
CD4+ lymphocytes in blood. In HIV-1 patients the number of CD4+lymphocytes is increased to normal
values after 2 weeks of therapy. Importantly, the 23-day periodicity of appearance of CD4+ lymphocytes
suggests that α1PI regulates adult human thymopoiesis.
Weill Medical College of Cornell University, New York, NY 10065, USA.