Cd4/Cd8

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Nat Rev Microbiol. Author manuscript; available in PMC 2009 August 17.
Published in final edited form as: Nat Rev Microbiol. 2008 November ; 6(11 Suppl): S7–15. doi:10.1038/nrmicro1998.

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CD4 immunophenotyping in HIV infection
David Barnett*, Brooke Walker‡, Alan Landay§, andThomas N. Denny‡ * UK NEQAS for Leukocyte Immunophenotyping, Rutledge Mews, 3 Southbourne Road, Sheffield, S10 2QN UK
‡

Center for HIV/AIDS Vaccine Immunology, Duke Human Vaccine Institute, Duke University Medical Center, 106 Research Drive, MSRB II, DUMC Box 103020, Durham, NC 27710, USA
§

Department of Immunology & Microbiology, Rush University Medical Center, 1735 West Harrison Street,Room 616 Cohn, Chicago, IL 60612, USA

Abstract
The ability to rapidly identify immune cell subsets such as CD4 cells, which became possible around the same time as the onset of the HIV/AIDS pandemic, was one of the greatest advances in clinical and diagnostic immunology. The evolution of this global pandemic and the subsequent development of treatment strategies to prolong the life of infectedindividuals mean that it is now more crucial than ever that we develop affordable, reliable and accurate methods for the enumeration of CD4 cells. Here, we provide an overview of the historical developments in CD4 enumeration technologies that are related to HIV infection, and summarize the current technological challenges that must be overcome to meet the needs of those living with HIVinfection. Recent figures from the World Health Organization (WHO) indicate that almost 33.2 million people are living with HIV infection worldwide, and over two-thirds of infected individuals are present in developing countries with limited resources (FIG. 1). In the region that has been hardest hit by AIDS — sub-Saharan Africa — the prevalence rate of HIV infection is 39%, yet only 17% of theHIV-infected individuals in this region had access to life-saving antiretroviral (ARV) therapy in 2007. Globally, more than 50% of those infected with HIV are women. Furthermore, recent reports from the WHO state that 1,800 babies are born with HIV every day because their mothers cannot access the necessary drugs or healthcare treatment. It is predicted that between 2008 and 2010 there will be 45 millionnew infections in resourceconstrained and middle-income countries if no additional preventative methods are introduced. It is now well recognized that, in the majority of cases, the development of AIDS parallels the decline in CD4+ T cells, which play a vital role in the regulation of the immune response. HIV specifically targets and binds to the CD4 antigen and chemokine receptor 5 (CCR5) or CXCchemokine receptor 4 (CXCR4) on CD4+ T cells to replicate, ultimately causing the destruction and deterioration of the immune system. The monitoring of CD4+ T cells during the course of HIV infection is therefore a crucial component in the monitoring of disease progression and the response to ARV therapy. Over the past 25 years there have been major technological advances in the ways that CD4+ Tcells are enumerated, with flow cytometry now generally regarded as the predicate technique. During this period, flow cytometry has progressed from large, expensive and complex fluorescence-activated cell sorting (FACS) machines that require highly specialized operating personnel, to smaller, more affordable bench-top instruments that can be used by individuals

Correspondence to D. B. e-mail:d.barnett@sheffield.ac.uk.

Barnett et al.

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with minimal training. This shift was made possible in part by including multicolour analysis coupled with simplified gating technologies. More recently, several low-cost, point of care, micro-diagnostic technologies have been developed for use in rural settings, however, full validation of these technologies is still awaited. In many...