Primary Human Immunodeficiency Virus Type 1-Specific CD8<sup>+</sup>T-Cell Responses Induced by Myeloid Dendritic Cells

Colleton, Bonnie A.; Huang, Xiaoli; Melhem, Nada M.; Zheng, Fan; Borowski, Luann; Rappocciolo, Giovanna; Rinaldo, Charles R.

doi:10.1128/jvi.02611-08

Cited by 29 publications

(40 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Responders with medium alone or with DC alone served as negative controls, and a peptide pool consisting of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and influenza virus (CEF) peptides was used as a positive control for both responder conditions. ELISpot plates were washed and processed as described previously (15,42). Spots were counted by using an automated ELISpot plate reader (AID, Strasberg, Germany) and are shown as the number of background-subtracted antigen-specific spot-forming cells (SFC) per 10 6 cells.…”

Section: Methodsmentioning

confidence: 99%

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1

Smith

Mailliard

Larsen

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune responses generated during infection. Current methods of identifying antigen-specific T cell reactivity in HIV-1 infection use bulk peripheral blood mononuclear cells (PBMC) yet ignore professional antigen-presenting cells (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants of major histocompatibility complex (MHC) class I-restricted epitopes from HIV-1 Gag and Env were used as antigens in gamma interferon (IFN-␥) enzyme-linked immunosorbent spot (ELISpot) and polyfunctional cytokine assays. Here we show that dendritic cells (DC) enhanced T cell reactivity at all stages of disease progression but specifically restored T cell reactivity after combination antiretroviral therapy (cART) to early infection levels. Type 1 cytokine secretion was also enhanced by DC and was most apparent late post-cART. We additionally show that DC reveal polyfunctional T cell responses after many years of treatment, when potential immunotherapies would be implemented. These data underscore the potential efficacy of DC immunotherapy that aims to awaken a dormant, autologous, HIV-1-specific CD8 ؉ T cell response. IMPORTANCEAssessment of endogenous HIV-1-specific T cell responses is critical for generating immunotherapies for subjects on cART. Current assays ignore the ability of dendritic cells to reveal these responses and may therefore underestimate the breadth and magnitude of T cell reactivity. As DC do not prime new responses in these assays, it can be assumed that the observed responses are not detected without appropriate stimulation. This is important because dogma states that HIV-1 mutates to evade host recognition and that CD8 ؉ cytotoxic T lymphocyte (CTL) failure is due to the inability of T cells to recognize the autologous virus. The results presented here indicate that responses to autologous virus are generated during infection but may need additional stimulation to be effective. Detecting the breadth and magnitude of HIV-1-specific T cell reactivity generated in vivo is of the utmost importance for generating effective DC immunotherapies.

show abstract

Section: Methodsmentioning

confidence: 99%

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1

Smith

Mailliard

Larsen

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…7 ART improved IFN␣ production by pDCs in response to TLR stimulation, but comparisons were not made to uninfected control pDCs. 7 Both DC subsets are highly efficient at stimulating HIV-specific T-cell responses, [9][10][11] and mDCs are capable of priming polyfunctional HIV-specific T-cell responses. 12 Interestingly, mDCs do not become activated upon stimulation with HIV.…”

Section: Introductionmentioning

confidence: 99%

Evidence of dysregulation of dendritic cells in primary HIV infection

Sabado

O’Brien

Subedi

et al. 2010

Blood

153

175

View full text Add to dashboard Cite

“…+ T cell help, as has been shown for induction of HIV-specific CD8 + T cells (24). This system provides the opportunity to investigate these factors.…”

Section: ) Expansion Of Multifunctional Cd8 + T Cells With Modcs Imentioning

confidence: 99%

“…Antigen-loaded moDCs are commonly used to induce and expand antigen-specific CD8 + T cells from PBMCs (24)(25)(26)(27). To compare the phenotypes and functional capacities of aAPCand moDC-expanded virus-specific CD8 + T cells, cells from three donors were stimulated with either peptide aAPCs or autologous peptide moDCs for 3 weeks.…”

mentioning

confidence: 99%

Dynamic regulation of functionally distinct virus-specific T cells

Ndhlovu

Oelke

Schneck

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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

show abstract

Primary Human Immunodeficiency Virus Type 1-Specific CD8⁺T-Cell Responses Induced by Myeloid Dendritic Cells

Cited by 29 publications

References 65 publications

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1

Evidence of dysregulation of dendritic cells in primary HIV infection

Dynamic regulation of functionally distinct virus-specific T cells

Contact Info

Product

Resources

About

Primary Human Immunodeficiency Virus Type 1-Specific CD8+T-Cell Responses Induced by Myeloid Dendritic Cells

Cited by 29 publications

References 65 publications

Dendritic Cells Restore CD8+T Cell Reactivity to Autologous HIV-1

Dendritic Cells Restore CD8+T Cell Reactivity to Autologous HIV-1

Evidence of dysregulation of dendritic cells in primary HIV infection

Dynamic regulation of functionally distinct virus-specific T cells

Contact Info

Product

Resources

About

Primary Human Immunodeficiency Virus Type 1-Specific CD8⁺T-Cell Responses Induced by Myeloid Dendritic Cells

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1

Dendritic Cells Restore CD8⁺T Cell Reactivity to Autologous HIV-1