The Impaired in Vitro Production of Interleukin-2 in HIV Infection Is Negatively Correlated to the Number of Circulating CD4+ DR+ T Cells and Is Reversed by Allowing T Cells to Rest in Culture: Arguments for in Vivo CD4+ T Cell Activation

1993 ◽  
Vol 67 (3) ◽  
pp. 185-191 ◽  
Author(s):  
O. Lees ◽  
S. Ramzaoui ◽  
D. Gilbert ◽  
F. Borsa ◽  
G. Humbert ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Cd4 T Cell ◽  
In Vitro Production ◽  
Vitro Production

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals Autologous Tumor Infiltrating T Cells Cytotoxic for Follicular Lymphoma Cells Can Be Expanded In Vitro

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3806-3816 ◽  
Author(s):  
Joachim L. Schultze ◽  
Mark J. Seamon ◽  
Sabine Michalak ◽  
John G. Gribben ◽  
Lee M. Nadler
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Autologous Tumor

Abstract Follicular lymphomas (FLs) rarely induce clinically significant T-cell–mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-γ, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL–specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.

scholarly journals CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production

1998 ◽  
Vol 188 (2) ◽  
pp. 287-296 ◽  
Author(s):  
Angela M. Thornton ◽  
Ethan M. Shevach
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Peripheral Tolerance ◽  
Cell Contact ◽  
Suppressor T Cells

Peripheral tolerance may be maintained by a population of regulatory/suppressor T cells that prevent the activation of autoreactive T cells recognizing tissue-specific antigens. We have previously shown that CD4+CD25+ T cells represent a unique population of suppressor T cells that can prevent both the initiation of organ-specific autoimmune disease after day 3 thymectomy and the effector function of cloned autoantigen-specific CD4+ T cells. To analyze the mechanism of action of these cells, we established an in vitro model system that mimics the function of these cells in vivo. Purified CD4+CD25+ cells failed to proliferate after stimulation with interleukin (IL)-2 alone or stimulation through the T cell receptor (TCR). When cocultured with CD4+CD25− cells, the CD4+CD25+ cells markedly suppressed proliferation by specifically inhibiting the production of IL-2. The inhibition was not cytokine mediated, was dependent on cell contact between the regulatory cells and the responders, and required activation of the suppressors via the TCR. Inhibition could be overcome by the addition to the cultures of IL-2 or anti-CD28, suggesting that the CD4+CD25+ cells may function by blocking the delivery of a costimulatory signal. Induction of CD25 expression on CD25− T cells in vitro or in vivo did not result in the generation of suppressor activity. Collectively, these data support the concept that the CD4+CD25+ T cells in normal mice may represent a distinct lineage of “professional” suppressor cells.

scholarly journals Autologous Tumor Infiltrating T Cells Cytotoxic for Follicular Lymphoma Cells Can Be Expanded In Vitro

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3806-3816 ◽  
Author(s):  
Joachim L. Schultze ◽  
Mark J. Seamon ◽  
Sabine Michalak ◽  
John G. Gribben ◽  
Lee M. Nadler
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Autologous Tumor

Follicular lymphomas (FLs) rarely induce clinically significant T-cell–mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-γ, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL–specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.

scholarly journals TRPM2 Is Not Required for T-Cell Activation and Differentiation

2022 ◽  
Vol 12 ◽  
Author(s):  
Niels C. Lory ◽  
Mikolaj Nawrocki ◽  
Martina Corazza ◽  
Joanna Schmid ◽  
Valéa Schumacher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Activation Markers

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+ signal that is crucial for T-cell function. The Ca2+ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+ through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived from in vitro studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+ signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulation in vitro, Trpm2-/- and WT CD4+ and CD8+ T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of Trpm2-/- CD8+ T cells and unimpaired differentiation of CD4+ T cells into Th1, Th17, and Treg cells under specific polarizing conditions. In vivo, Trpm2-/- and WT CD8+ T cells showed equal specific responses to Listeria monocytogenes after infection of WT and Trpm2-/- mice and after transfer of WT and Trpm2-/- CD8+ T cells into infected recipients. CD4+ T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT and Trpm2-/- CD4+ T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.

scholarly journals Antigen-independent activation of naive and memory resting T cells by a cytokine combination.

1994 ◽  
Vol 180 (3) ◽  
pp. 1159-1164 ◽  
Author(s):  
D Unutmaz ◽  
P Pileri ◽  
S Abrignani
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Effector Function ◽  
Necrosis Factor Alpha ◽  
Naive T Cells ◽  
Naïve T Cells

We investigated whether human resting T cells could be activated to proliferate and display effector function in the absence of T cell receptor occupancy. We report that combination of interleukin 2 (IL-2), tumor necrosis factor alpha, and IL-6 activated highly purified naive (CD45RA+) and memory (CD45RO+) resting CD4+ T cells to proliferate. Under this condition, memory resting T cells could also display effector function as measured by lymphokine synthesis and help for immunoglobulin production by B cells. This novel Ag-independent pathway of T cell activation may play an important role in vivo in recruiting effector T cells at the site of immune response and in maintaining the clonal size of memory T cells in the absence of antigenic stimulation. Moreover, cytokines can induce proliferation of naive T cells without switch to memory phenotype and this may help the maintenance of the peripheral pool of naive T cells.

scholarly journals Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip fromHerpesvirus saimiri

2015 ◽  
Vol 2015 ◽  
pp. 1-12
Author(s):  
Jean-Paul Vernot ◽  
Ana María Perdomo-Arciniegas ◽  
Luis Alberto Pérez-Quintero ◽  
Diego Fernando Martínez
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lipid Rafts ◽  
T Cell Activation ◽  
Cell Activation ◽  
Jurkat Cells ◽  
Chimeric Peptide ◽  
Vector Targeting

The Lck interacting protein Tip ofHerpesvirus saimiriis responsible for T-cell transformation bothin vitroandin vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human andAotussp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts.

scholarly journals Contact-dependent delivery of IL-2 by dendritic cells to CD4 T cells in the contraction phase promotes their long-term survival

2019 ◽  
Vol 11 (2) ◽  
pp. 108-123
Author(s):  
Dan Tong ◽  
Li Zhang ◽  
Fei Ning ◽  
Ying Xu ◽  
Xiaoyu Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Immune Memory ◽  
Term Survival

Abstract Common γ chain cytokines are important for immune memory formation. Among them, the role of IL-2 remains to be fully explored. It has been suggested that this cytokine is critically needed in the late phase of primary CD4 T cell activation. Lack of IL-2 at this stage sets for a diminished recall response in subsequent challenges. However, as IL-2 peak production is over at this point, the source and the exact mechanism that promotes its production remain elusive. We report here that resting, previously antigen-stimulated CD4 T cells maintain a minimalist response to dendritic cells after their peak activation in vitro. This subtle activation event may be induced by DCs without overt presence of antigen and appears to be stronger if IL-2 comes from the same dendritic cells. This encounter reactivates a miniature IL-2 production and leads a gene expression profile change in these previously activated CD4 T cells. The CD4 T cells so experienced show enhanced reactivation intensity upon secondary challenges later on. Although mostly relying on in vitro evidence, our work may implicate a subtle programing for CD4 T cell survival after primary activation in vivo.

T cell-T cell activation in multiple sclerosis

1997 ◽  
Vol 3 (4) ◽  
pp. 238-242 ◽  
Author(s):  
JW Lindsey ◽  
RH Kerman ◽  
JS Wolinsky
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Viral Infections ◽  
Activated T Cells ◽  
In Vitro Proliferation

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

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