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Polychromatic immunophenotypic characterization of T cell profiles among HIV-infected patients experiencing immune reconstitution inflammatory syndrome (IRIS)

David M Murdoch1 email, Melinda S Suchard2 email, Willem DF Venter3 email, Patrick Mhlangu4 email, Janet S Ottinger5 email, Charles Feldman6 email, Annelies Van Rie7 email, Deborah K Glencross2,4 email, Wendy S Stevens2 email and Kent J Weinhold5 email

Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA

Department of Molecular Medicine and Haematology, University of the Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa

Reproductive Health & HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa

Contract Laboratory Services, Johannesburg, South Africa

Department of Surgery and Immunology and the Duke University Center for AIDS Research (CFAR), Duke University, Durham, North Carolina, USA

Division of Pulmonology, Department of Medicine, Johannesburg Hospital and University of the Witwatersrand, Johannesburg, South Africa

Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

author email corresponding author email

AIDS Research and Therapy 2009, 6:16doi:10.1186/1742-6405-6-16

Published: 16 July 2009

Abstract

Objective

To immunophenotype CD4+ and CD8+ T cell sub-populations in HIV-associated immune reconstitution inflammatory syndrome (IRIS).

Design

Nested case-control immunological study.

Methods

ART-naïve HIV-infected patients were prospectively observed for IRIS during the first 6 months of ART. Twenty-two IRIS cases and 22 ART-duration matched controls were sampled for T cell immunophenotyping.

Results

IRIS cases demonstrated significantly lower CD4 cell counts compared to controls (baseline: 79 versus 142, p = 0.02; enrollment: 183 versus 263, p = 0.05, respectively) with no differences in HIV RNA levels. Within CD4+T cells, cases exhibited more of an effector memory phenotype compared to controls (40.8 versus 27.0%, p = 0.20), while controls trended towards a central memory phenotype (43.8 versus 30.8%, p = 0.07). Within CD8+ T cells, controls exhibited more central memory (13.9 versus 7.81%, p = 0.01, respectively) and effector (13.2 versus 8.8%, p = 0.04, respectively) phenotypes compared to cases, whereas cases demonstrated more terminal effectors than controls (28.8 versus 15.1%, p = 0.05). Cases demonstrated increased activation of CD8+ T cell effector memory, terminal effector, and effector subsets than controls (p = 0.04, 0.02, and 0.02, respectively).

Conclusion

CD4+ and CD8+ T cell subset maturational phenotypes were heterogeneous among IRIS cases and controls. However, IRIS cases demonstrated significant increases in activation of CD8+ T cell effector subpopulations.


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