Dynamic regulation of functionally distinct virus-specific T cells

Abstract

The functional capacities of CD8 + T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4 + T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8 + T cells specific for two different virus antigens stimulated ex vivo using either autologous monocytederived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8 + T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8 + T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8 + T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8 + T cell function.antigen presenting cells | CD8 T cells | viral immunity | multifunctional T cells

Sprouty-2 regulates HIV-specific T cell polyfunctionality

“…The generation of moDCs was done by following the standard protocol as previously described (28,43). Briefly, CD14 + cells were cultured in complete RPMI supplemented with 5% autologous plasma, 100 ng/ml human granulocyte-macrophage colonystimulating factor, and 50 ng/ml IL-4.…”

A high-throughput single-cell analysis of human CD8+ T cell functions reveals discordance for cytokine secretion and cytolysis

“…CD8 + CTLs are a prominent component of the adaptive immune response that contributes to the clearance of viruses in acute infection (1). Antigen-specific CD8 + T cells can exhibit a range of functions, including the production of effector cytokines, degranulation, cytolytic activity, suppression of viral replication, and proliferation upon exposure to cells presenting antigen (2)(3)(4).…”

T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool

“…[1][2][3][4] The molecular signals that orchestrate the function and diversification of effector and memory CD8 ϩ T-cell subsets downstream of these receptors are beginning to be elucidated and how T-cell receptor (TCR) signals affect CD8 ϩ T-cell effector function and fate choices is not fully understood. [5][6][7][8][9][10][11][12][13][14] The CD8 ϩ effector T-cell pool can be divided into terminally differentiated, short-lived KLRG-1 hi IL-7r␣ lo effector cells (SLECs) and less differentiated KLRG-1 lo IL-7r␣ hi memory precursor cells (MPECs). 3,[15][16][17] SLECs typically produce the effector cytokine interferon␥ (IFN␥) and may also coproduce tumor necrosis factor␣ (TNF␣) in response to antigen but only memory precursors can produce interleukin-2 (IL-2) in addition to IFN␥ and TNF␣.…”