Abstract
CD4+ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4+ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4+ T cells are further segregated into central, effector and transitional memory cell subsets by functional, phenotypic and homeostatic characteristics. Defining the distribution of HIV-1 infection in different T cell subsets is important, as this can play a role in determining the size and composition of the viral reservoir. Both central memory and transitional memory CD4+ T cells have been described as long-lived viral reservoirs for HIV. Recently, the newly described stem memory T cell subset has also been implicated as a long-lived HIV reservoir. Using green fluorescent protein (GFP) reporter strains of HIV-1 and multi parameter flow cytometry, we developed an assay to simultaneously quantify the susceptibility of stem memory (TSCM), central memory, effector memory, transitional memory and naïve CD4+ T cell subsets, to HIV-1 infection in vitro. We show that TSCM are susceptible to infection with laboratory adapted and clinical HIV-1 strains. Our system facilitates the quantitation of HIV-1 infection in alternative T cell subsets by CCR5- and CXCR4-using viruses across different HIV-1 subtypes, and will be useful for studies of HIV-1 pathogenesis and viral reservoirs.
Highlights
Memory T cells play an important part of the adaptive immune response to infection [1,2,3]
We previously developed an assay to quantify human immunodeficiency virus type 1 (HIV-1) infection in non-TSCM CD4+ T cell subsets in vitro [21]
Since the recent description of TSCM cells, we have developed a new assay system which incorporates quantitation of HIV-1 infection in the TSCM subset
Summary
Memory T cells play an important part of the adaptive immune response to infection [1,2,3]. TSCM are antigen-experienced and upon TCR stimulation, exhibit effector activity and are able to differentiate into CM and EM subsets They have the ability to self-renew in the presence of IL-15 homeostatic signals, and are able to survive for longer periods than CM or EM populations [12]. In HIV-1, CD4+ T cells are a key target of infection, where depletion of these cells results in deterioration of the immune system and progression to AIDS [14,15] Both CM and TM CD4+ T cell subsets have been demonstrated as major HIV-1 cellular reservoirs where the maintenance of these reservoirs is associated with T cell survival and homeostatic proliferation (antigen-driven and IL-7-mediated, respectively) [8]. T cells during disease pathogenesis, and characterizes changes in tropism between CCR5- and CXCR4-using viruses is important for the design of new therapeutic targets and for characterizing the cellular reservoir of HIV-1
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