Chapter 6

α1Antitrypsin Therapy Increases CD4+ Lymphocytes to Normal Values in HIV-1 Patients

Cynthia L. Bristow, Jose Cortes, Roya Mukhtarzad, Maylis Trucy, Aaron Franklin, Val Romberg and Ronald Winston

Abstract

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.

Total Pages: 102-110 (9)

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