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Immunology - Infectious Diseases - Urology


Progressive Activation of CD127+132- Recent Thymic Emigrants into Terminally Differentiated CD127-132+ T-Cells in HIV-1 Infection
Published: Monday, February 13, 2012
Author: Sarah C. Sasson et al.

by Sarah C. Sasson, John J. Zaunders, Nabila Seddiki, Michelle Bailey, Kristin McBride, Kersten K. Koelsch, Kate M. Merlin, Don E. Smith, David A. Cooper, Anthony D. Kelleher

Aim

HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation.

Methods

Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured.

Results

CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2low and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs.

Conclusion

The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis.

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