Virus Infection Stages and Distinct Th1 or Th17/Th22 T-Cell Responses in Malaria/SHIV Coinfection Correlate with Different Outcomes of Disease

Ryan-Payseur, Bridgett; Ali, Zahida; Huang, Dan; Chen, Crystal Y.; Lin, Yan; Wang, Richard C.; Collins, William E.; Wang, Yunqi; Chen, Zheng W.

doi:10.1093/infdis/jir549

Cited by 28 publications

(36 citation statements)

References 41 publications

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“…Since mouse IFNγ and perforin are needed for anti-TB immunity [23], [24], [25], [26] and human granulysin kills Mtb [4], we examined if these anti-TB cytokines could be produced by Picostim-expanded Vγ2Vδ2 T cells in the pulmonary compartment. We employed both the conventional intracellular cytokine staining(ICS) upon in vitro antigen stimulation and the modified direct ICS assay without in vitro antigen stimulation since the direct ICS assay had been demonstrated to be useful for measuring T effector cells that were close to the in vivo setting during infections [22], [27], [28], [29], [30]. We found that appreciable numbers of Vγ2Vδ2 T cells in the pulmonary compartment were able to re-recognize HMBPP phosphoantigen and produce IFNγ over time after the Picostim/IL-2 administration(Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Direct ICS was adapted from the conventional ICS protocol, and the major modification was that PBMC or BAL cells were directly measured by ICS for intracellular cytokines without prior in vitro Ag stimulation as we recently described [17], [27], [28], [29], [44]. Direct ICS approach was characterized and validated extensively in vitro and in vivo conditions as we previously reported [17], [22], [27], [28], [29], [30].…”

Section: Methodsmentioning

confidence: 99%

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Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

et al. 2013

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Dominant Vγ2Vδ2 T-cell subset exist only in primates, and recognize phosphoantigen from selected pathogens including M. tuberculosis(Mtb). In vivo function of Vγ2Vδ2 T cells in tuberculosis remains unknown. We conducted mechanistic studies to determine whether earlier expansion/differentiation of Vγ2Vδ2 T cells during Mtb infection could increase immune resistance to tuberculosis in macaques. Phosphoantigen/IL-2 administration specifically induced major expansion and pulmonary trafficking/accumulation of phosphoantigen-specific Vγ2Vδ2 T cells, significantly reduced Mtb burdens and attenuated tuberculosis lesions in lung tissues compared to saline/BSA or IL-2 controls. Expanded Vγ2Vδ2 T cells differentiated into multifunctional effector subpopulations capable of producing anti-TB cytokines IFNγ, perforin and granulysin, and co-producing perforin/granulysin in lung tissue. Mechanistically, perforin/granulysin-producing Vγ2Vδ2 T cells limited intracellular Mtb growth, and macaque granulysin had Mtb-bactericidal effect, and inhibited intracellular Mtb in presence of perforin. Furthermore, phosphoantigen/IL2-expanded Vγ2Vδ2 T effector cells produced IL-12, and their expansion/differentiation led to enhanced pulmonary responses of peptide-specific CD4+/CD8+ Th1-like cells. These results provide first in vivo evidence implicating that early expansion/differentiation of Vγ2Vδ2 T effector cells during Mtb infection increases resistance to tuberculosis. Thus, data support a rationale for conducting further studies of the γδ T-cell-targeted treatment of established TB, which might ultimately help explore single or adjunctive phosphoantigen expansion of Vγ2Vδ2 T-cell subset as intervention of MDR-tuberculosis or HIV-related tuberculosis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

et al. 2013

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“…This was done exactly the same as we previously described (36, 38, 45). Briefly, 10 6 PBMC, 10 6 or 3–5 ×10 5 lymphocytes (depending on availability) from BAL fluid or lung tissues were used in each reaction (round bottom 96-well plate) to measure T cells and CD3-negative lymphocytes that could constitutively produce IFNγ, TNFα, IL-17, IL-22, IL-4, and perforin without Ag stimulation in vitro .…”

Section: Methodsmentioning

confidence: 99%

“…As another control setting, PBL were collected weekly or bi-weekly for up to 3 months from 2 uninfected healthy macaques and 4 SHIV-infected macaques, and assessed for de novo production of IFN-γ, IL-17, and IL-22 over time using the direct ICS approach without Ag stimulation in vitro. T cells from these controls gave rise to no or very low levels of cytokines stained by this direct ICS methods (36, 38, 45). …”

Section: Methodsmentioning

confidence: 99%

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CD4+ T Cells Contain Early Extrapulmonary Tuberculosis (TB) Dissemination and Rapid TB Progression and Sustain Multieffector Functions of CD8+ T and CD3− Lymphocytes: Mechanisms of CD4+ T Cell Immunity

Shan

Huang

Chen

et al. 2014

The Journal of Immunology

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The possibility that CD4+ T cells can act as “innate-like” cells to contain very-early M. tuberculosis (Mtb) dissemination and function as master helpers to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes during development of adaptive immunity against primary tuberculosis(TB) has not been demonstrated. We showed that pulmonary Mtb infection of CD4-depleted macaques surprisingly led to very-early extrathoracic Mtb dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. CD4 depletion during Mtb infection revealed the ability of CD8+ T cells to compensate and rapidly differentiate to Th17-like/Th1-like, and cytotoxic-like effectors, but these effector functions were subsequently unsustainable due to CD4 deficiency. While CD3-negative non-T lymphocytes in presence of CD4+ T cells developed predominant Th22-like and NK-like (perforin production) responses to Mtb infection, CD4 depletion abrogated these Th22-/NK-like effector functions and favored IL-17 production by CD3-negative lymphocytes. CD4-depleted macaques exhibited no or few pulmonary T effector cells constitutively producing IFN-γ, TNFα, IL-17, IL-22, and perforin at the endpoint of more severe TB, but presented pulmonary IL-4+ T effectors. TB granulomas in CD4-depleted macaques contained fewer IL-22+ and perforin+ cells despite presence of IL-17+ and IL-4+ cells. These results implicate previously-unknown “innate-like” ability of CD4+ T cells to contain extrathoracic Mtb dissemination at very early stage. Data also suggest that CD4+ T cells are required to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes and to prevent rapid TB progression during Mtb infection of nonhuman primates.

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Experimental systems for studying Plasmodium/HIV coinfection

Frischknecht

Fackler

2016

FEBS Letters

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Edited by Wilhelm JustCoinfections with Human Immunodeficiency Virus (HIV) and Plasmodium, the causative agents of AIDS and malaria, respectively, are frequent and their comorbidity especially in sub-Saharan Africa is high. While clinical studies suggest an influence of the two pathogens on the outcome of the respective infections, experimental studies on the molecular and immunological impact of coinfections are rare. This reflects the limited availability of suitable model systems that reproduce key properties of both pathologies. Here, we discuss key aspects of coinfection with a focus on currently established experimental systems, their limitations for coinfection studies and potential strategies for their improvement.

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Virus Infection Stages and Distinct Th1 or Th17/Th22 T-Cell Responses in Malaria/SHIV Coinfection Correlate with Different Outcomes of Disease

Abstract: These novel findings suggest that virus infection status and selected Th1 or Th17/Th22 responses after malaria/AIDS-virus coinfection correlate with distinct outcomes of virus infection and malaria.

Cited by 28 publications

References 41 publications

Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

CD4+ T Cells Contain Early Extrapulmonary Tuberculosis (TB) Dissemination and Rapid TB Progression and Sustain Multieffector Functions of CD8+ T and CD3− Lymphocytes: Mechanisms of CD4+ T Cell Immunity

Experimental systems for studying Plasmodium/HIV coinfection

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