scholarly journals Clonal expansion of T cells: a cytotoxic T-cell response in vivo that involves precursor cell proliferation.

1986 ◽  
Vol 83 (16) ◽  
pp. 6089-6092 ◽  
Author(s):  
F. Denizot ◽  
A. Wilson ◽  
F. Battye ◽  
G. Berke ◽  
K. Shortman
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Clonal Expansion ◽  
T Cell Response ◽  
Precursor Cell ◽  
Cytotoxic T Cell

scholarly journals Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells.

1978 ◽  
Vol 147 (4) ◽  
pp. 1236-1252 ◽  
Author(s):  
T J Braciale ◽  
K L Yap
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Response ◽  
Infectious Virus ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell

This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.

scholarly journals The Primary in vivo Murine Cytotoxic T Cell Response to the Flavivirus, West Nile

1987 ◽  
Vol 68 (7) ◽  
pp. 2001-2006 ◽  
Author(s):  
A. M. Kesson ◽  
R. V. Blanden ◽  
A. Mullbacher
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
West Nile

scholarly journals Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

1990 ◽  
Vol 171 (5) ◽  
pp. 1815-1820 ◽  
Author(s):  
P Aichele ◽  
H Hengartner ◽  
R M Zinkernagel ◽  
M Schulz
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Lymphocytic Choriomeningitis ◽  
Effector T Cells ◽  
T Cell Response ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Effector T Cell

Induction in vivo of antiviral cytotoxic T cell response was achieved in a MHC class I-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in IFA. The effector T cells are CD8+, restricted to the class I Ld allele of the analyzed mouse strain, and are specific both at the level of secondary restimulation in vitro and at the effector T cell level. These results suggest that cocktails of viral peptides may be used as antiviral T cell vaccines.

Loss of EBV-Specific CD4+T Cells during Progression to EBV-Related AIDS Non-Hodgkin Lymphoma: Restoration by Highly Active Antiretroviral Therapy (HAART).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3110-3110
Author(s):  
Erwan R. Piriou ◽  
Christine Jansen ◽  
Karel van Dort ◽  
Iris De Cuyper ◽  
Nening M. Nanlohy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Antigen Processing ◽  
Ex Vivo ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Numbers

Abstract Objective: EBV-specific CD8+ T cells have been extensively studied in various settings, and appear to play a major role in the control of EBV-related malignancies. In contrast, it is still unclear whether EBV-specific CD4+ T cells play a role in vivo. To study this question, an assay was developed to measure the CD4+ T-cell response towards two EBV antigens, in both healthy (n=14) and HIV-infected subjects (n=23). In addition, both HAART-treated (n=12) and untreated HIV+ individuals (n=14) - including progressors to EBV-related lymphoma - were studied longitudinally. Methods: EBV-specific CD4+ T cells were stimulated with peptide pools from latent protein EBNA1 and lytic protein BZLF1, and detected by measurement of IFNg-production. Results: After direct ex vivo stimulation, EBNA1 or BZLF1-specific IFNg- (and/or IL2) producing CD4+ T cell numbers were low, and measurable in less than half of the subjects studied (either HIV- and HIV+). Therefore, PBMC were cultured for 12 days in the presence of peptides and IL2 (from day 3), and then restimulated with peptides, allowing specific and reproducible expansion of EBV-specific CD4+ T cells, independent of HLA type and ex vivo antigen processing. Interestingly, numbers of EBV-specific CD4+ T cells inversely correlated with EBV viral load, implying an important role for EBV-specific CD4+ T cells in the control of EBV in vivo. Untreated HIV-infected individuals had a lower CD4+ T cell response to EBNA1 and BZLF1 as compared to healthy EBV carriers and HAART-treated HIV+ subjects. In longitudinal samples, EBNA1-specific, but not BZLF1-specific T-cell numbers increased after HAART, while EBV load was not affected by treatment. In all the progressors to EBV-related lymphoma, EBV-specific CD4+ T cells were lost at least 24 months before lymphoma diagnosis. Conclusions: Both cross-sectional and longitudinal data suggest an important role for EBV-specific CD4+ T cells in the control of EBV-related malignancies. Furthermore, it seems that HAART treatment leads to recovery of EBNA1-specific, but not BZLF1-specific CD4+ T-cell responses, implying changes in the latency pattern of EBV, despite an unaltered cell-associated EBV DNA load. Thus, early HAART treatment might prevent loss of specific CD4+ T-cell help and progression to NHL.

scholarly journals Presentation of the H-Y antigen on Langerhans' cell-negative corneal grafts downregulates the cytotoxic T cell response and converts responder strain mice into phenotypic nonresponders.

1988 ◽  
Vol 168 (5) ◽  
pp. 1749-1766 ◽  
Author(s):  
J S Peeler ◽  
D G Callanan ◽  
M W Luckenbach ◽  
J Y Niederkorn
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Langerhans Cells ◽  
Antigen Expression ◽  
T Cell Response ◽  
T Helper Cell ◽  
Cytotoxic T Cell ◽  
T Helper ◽  
Active Suppression

We have used the murine cornea is an allograft model to investigate the relative roles of graft-derived IA+ APC (Langerhans' cells) and host-derived APC during the induction of CTL responses to H-Y. The natural exclusion of LC from the immunizing corneal graft led to a specific state of unresponsiveness to H-Y in responder strain mice, while inclusion of LC resulted in responsiveness. Failure to respond to H-Y could not be attributed to the absence of H-Y or IA antigen expression on the surface of LC-deficient grafts but instead, appeared to be due to active suppression of the T helper cell response during in vivo priming. Reprocessing of the H-Y antigen by host APC did not occur after immunization with H-Y presented on H-2-incompatible grafts unless presented initially by graft-derived LC. H-2 as well as some non-H-2 alloantigens were presented to the host without a requirement for donor-derived LC. Thus there appear to be differential requirements for the processing and presentation of alloantigens.

132. IMMUNE-DEVIATING CYTOKINES DETERMINE THE MATERNAL T CELL RESPONSE DURING PREGNANCY AND TOLERANCE OR REJECTION OF THE CONCEPTUS

2009 ◽  
Vol 21 (9) ◽  
pp. 51
Author(s):  
L. M. Moldenhauer ◽  
J. D. Hayball ◽  
S. A. Robertson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Tolerance ◽  
Cell Response ◽  
Fetal Loss ◽  
T Cell Response ◽  
Cell Phenotype ◽  
Fetal Survival

In healthy pregnancies the maternal immune system establishes paternal antigen-specific tolerance allowing survival of the semi-allogeneic conceptus. The cytokine environment is a key factor in determining the phenotype of antigen-specific lymphocytes, influencing the development of either cytotoxic or tolerogenic cells. We hypothesized that the cytokine environment at the time of priming to paternal antigens influences the phenotype of the maternal T cell response and pregnancy outcome. Transgenic Act-mOVA male mice expressing chicken ovalbumin (OVA) ubiquitously provided OVA as a model paternal antigen. OVA is present within the semen of Act-mOVA mice and is inherited and expressed by the conceptus tissue. OVA-reactive CD8+ OT-I T cells were activated with OVA in the presence of various immune-deviating cytokines in vitro, before transfer at 3.5 dpc to C57Bl/6 (B6) females gestating OVA-expressing fetuses. Pregnant mice received either naïve OT-I T cells, cytotoxic OT-I T cells stimulated in vitro in the presence of IL-2 or OT-I T cells stimulated in vitro in the presence of TGFβ1 and IL-10, two factors present in the uterus and associated with immune tolerance. Immunohistochemistry was utilized to demonstrate that OT-I T cells infiltrate into the implantation site. Cytotoxic OT-I T cells caused fetal loss, while OT-I T cells activated in vivo or in vitro with TGFβ1 and IL-10 did not cause fetal loss. Additionally, cytotoxic OT-I T cells did not affect B6 x B6 matings, demonstrating the antigen-specific nature of the T cell-mediated fetal loss. Collectively these experiments show that maternal antigen-reactive T cells activated in vivo in the cytokine environment of the mated uterus are tolerogenic, not cytotoxic, and implicate TGFβ1 and IL-10 as key elements of that environment. We conclude that the cytokine environment at the time of priming to paternal antigens influences the T cell phenotype and impacts upon maternal immune tolerance and fetal survival.

Cord Blood Nucleated Cells Induce Delayed Proliferative and Cytotoxic T Cell Alloreactivity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5138-5138
Author(s):  
Dolores Mahmud ◽  
Sandeep Chunduri ◽  
Javaneh Abbasian ◽  
John Maciejewski ◽  
Ronak Iqbal ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Proliferation ◽  
Cd34 Cells ◽  
Ctl Activity

Abstract Transplantation of HLA-mismatched nucleated cells from cord blood (CB) has reduced risks of graft rejection and severe acute graft-versus-host disease. In this study we analyzed the in-vitro alloantigen presenting capacity of cord blood nucleated cells. CB mononuclear cells (MNCs) or immunomagnetically-selected CD34+ cells, or CD14+ monocytes, were irradiated and tested as stimulators of allogeneic blood T cells in primary (stimulator:responder ratio = 1:1) or secondary (stimulator:responder ratio = 1:2) mixed leukocyte culture (MLC), or in cytotoxic T-lymphocytes (CTL) assays. CB-MNCs failed to induce allogeneic T cell proliferation in 6-days primary MLC, whereas CD34+ or CD14+ cells stimulated brisk T cell responses. A suppressive effect of CB-MNCs was ruled out since CD3+ cell-depletion of CB-MNCs did not restore CB immunogenicity and the addition of increasing doses of CB-MNCs did not inhibit T cell alloreactivity to CD34+ cells. Despite allogeneic T cells were unresponsive to CB-MNCs after primary and secondary MLC, T cell anergy was ruled out since T cells that were unresponsive after primary MLC proliferated potently in secondary MLC stimulated with CB CD34+ cells, and even more with CB monocyte-derived dendritic cells (Mo-DC) generated in-vitro with GM-CSF and IL-4. Interestingly, after co-culture with irradiated allogeneic T cells for 6 days, CB-MNCs showed a greater proportion of CD86+ cells and elicited allo- T cell proliferation. In addition, allo-CTL activity was induced by CB-MNCs only after restimulating effector cells for 3–4 weeks (26±7% lysis of antigen-specific PHA-blast at 50:1 E:T ratio), and was comparable to CTL activity induced after 1 week by Mo-DC generated from the same CB. When T cell effectors were stimulated by combining two incompatible cord blood MNCs mixed together, CTL activity was then detected after 4 weeks against both of them regardless of the CB:CB cell ratio. These results show an impaired allo-APC activity of CB-MNCs, without suppressive or tolerogenic activity. These findings might partially explain the initial engraftment of combined HLA mismatched CB grafts in vivo, however they also suggest that a delayed T cell response may occur due to CB-derived APCs activating CTLs.

Impact of Regulatory T Cells on Antigen Specific T Cell Response Using Recombinant Chimeric T Cell Receptors In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5475-5475
Author(s):  
David M. Kofler ◽  
Markus Chmielewski ◽  
Heike Koehler ◽  
Tobias Riet ◽  
Patrick Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
T Cell Receptors ◽  
Cell Response ◽  
Effector T Cells ◽  
T Cell Response ◽  
Cell Receptors

Abstract Recombinant T cell receptors with defined specificity against tumor cells are a promising experimental approach in the elimination of residual leukemia and lymphoma cells. It is so far unresolved whether regulatory T cells with suppressor activities impair the efficiency of cytolytic T cells grafted with a recombinant immunoreceptor. The frequency of regulatory T cells is highly increased in tumor patients and their suppressive function seems to play a role in the fail of an autologous T cell response against the malignant cells. In this study we analyzed the antigen-triggered, specific activation of receptor grafted T cells in the presence or absence of regulatory CD4+CD25high T cells. CD3+ T cells were grafted with CEA-specific immunoreceptors containing the CD3-zeta signaling domain for T cell activation. Co-cultivation of receptor grafted effector T cells together with regulatory T cells repressed proliferation of the effector cells and decreased IL-2 secretion. Secretion of IFN-gamma and IL-10 was not impaired. Interestingly, the cytotoxicity of grafted effector T cells towards CEA-expressing tumor cells was not impaired by regulatory T cells in vitro. To evaluate the relevance in vivo, we used a Crl:CD1 Nu/Nu mouse model to assess growth of CEA+ tumor cells in the presence of receptor grafted effector T cells and of regulatory T cells. Mice inoculated with tumor cells together with CD3+ effector T cells without immunoreceptor and regulatory T cells developed earlier tumors with faster growth kinetics compared to mice that were inoculated with tumor cells, CD3+ T cells and CD4+CD25- control T cells. Using effector T cells that were equipped with a recombinant CEA-specific CD3-zeta immunoreceptor, 2 of 5 mice developed a tumor in the presence of regulatory T cells while none of the mice developed a tumor in the absence of regulatory T cells. Taken together, regulatory T cells obviously impair an antigen-specific, anti-tumor T cell attack in vivo. This seems to be due to repression of proliferation of the effector T cells and not to diminished cytotoxicity. These findings have major impact on the design of clinical studies involving adoptively transferred effector T cells.

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