scholarly journals Dissecting human T cell responses against Bordetella species.

1988 ◽  
Vol 168 (4) ◽  
pp. 1351-1362 ◽  
Author(s):  
M T De Magistris ◽  
M Romano ◽  
S Nuti ◽  
R Rappuoli ◽  
A Tagliabue
Keyword(s):  
T Cell ◽  
Whooping Cough ◽  
T Cell Memory ◽  
T Cell Clones ◽  
Cell Responses ◽  
Human T Cell ◽  
Cell Clones ◽  
Specific Antigens ◽  
New Generation

To identify the minimal structures that may be important for the creation of a synthetic and/or recombinant vaccine against whooping cough, human T cell clones were obtained against Bordetella antigens. Cloned peripheral blood T lymphocytes from an immune donor were grown in IL-2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis, and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the 12 clones obtained into four groups with the following specificity: (1) filamentous hemagglutinin (FHA); (2) B. pertussis-specific antigens; (3) virulence-associated Bordetella-specific antigens; and (4) nonvirulence-associated Bordetella-specific antigens. Using two new B. pertussis deletion mutants, clone 6 (representative of cluster 1) was found to recognize the COOH terminus of FHA. Furthermore, three out of four clones of cluster 3 were specifically stimulated by the soluble 69-kD protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized pertussis toxin (PT), which is believed to be the most important protein to be included in an acellular vaccine. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria, although T cell memory against PT exists in a donor who had the disease several years ago.

Establishing T Cell Memory by Adoptive Transfer of T Cell Clones.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 866-866
Author(s):  
Carolina Berger ◽  
Michael C. Jensen ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Annexin V ◽  
T Cell Memory ◽  
T Cell Clones ◽  
Cell Clones

Abstract Adoptive transfer of T cells has been employed to reconstitute T cell immunity to viruses such as cytomegalovirus (CMV) in immunodeficient allogeneic stem cell transplant (SCT) patients and is being investigated to treat malignancies. In the allogeneic SCT setting, the T cells are derived from the donor and need to be isolated as clones or highly pure populations to avoid graft-versus-host disease. CD8+ T cells can be divided into defined subsets including CD62L− effector memory (TEM) and central memory T cells (TCM) expressing the CD62L lymph node homing molecule. Both TCM and TEM can give rise to cytolytic effector T cells (TE) after antigen stimulation and can be expanded in vitro for immunotherapy. However, the potential of T cells derived from either the TEM or TCM subset to persist in vivo has not been investigated. We used a macaque model to determine whether reconstitution of T cell memory to CMV by adoptive transfer of CD8+ T cell clones depended on their origin from either the CD62L+ TCM or CD62L− TEM subset. T cell clones were retrovirally transduced to express the macaque CD19 or CD20 surface marker to allow tracking of T cells in vivo. Clones derived from both TCM and TEM had similar avidity and proliferative capacity in vitro, and had a TE phenotype (CD62L−CCR7−CD28−CD127−, granzyme B+). TCM and TEM-derived T cell clones were transferred to macaques at doses of 3–6×108/kg and were both detected in the blood one day after transfer at 1.2–2.7% (low dose) to 20–25% (high dose) of CD8+ T cells. However, the frequency of TEM-derived T cells was undetectable after 3–5 days, and the cells were not present in lymph node or bone marrow obtained at day 14. By contrast, TCM-derived clones persisted in peripheral blood, migrated to tissue sites, and were detectable long-term at significant levels. A distinguishing feature of TCM-derived cells was their responsiveness to homeostatic cytokines. Only TCM-derived clones were rescued from apoptotic cell death by low-dose IL15 for >30 days in vitro and this correlated with higher levels of IL15Rα, IL2Rβ, and IL2Rγ, and of Bcl-xL and Bcl-2, which promote cell survival. To determine if the inability of TEM-derived clones to survive in vitro correlated with an increased susceptibility of cell death in vivo, we measured the proportion of infused cells that were positive for propidium iodide (PI) and Annexin V during the short period of in vivo persistence. One day after transfer, 41–45% of TEM-derived T cells were Annexin V+/PI+, analyzed directly in the blood or after 24 hours of culture. By contrast, only a minor fraction of an adoptively transferred TCM-derived T cell clone was Annexin V+/PI+ and the infused cells survived in vivo. A subset of the persisting T cells reacquired TCM marker (CD62L+CCR7+CD127+CD28+) in vivo and regained functional properties of TCM (direct lytic activity; rapid proliferation to antigen). These T cells produced IFN-γ and TNF-α after peptide stimulation, and studies are in progress to assess their in vivo response to antigen by delivery of T cells expressing CMV proteins. Our studies in a large animal model show for the first time that CD8+ TE derived from TCM but not TEM can persist long-term, occupy memory T cell niches, and restore TCM subsets of CMV-specific immunity. Thus, taking advantage of the genetic programming of cells that have become TCM might yield T cells with greater therapeutic activity and could be targeted for human studies of T cell therapy for both viral and malignant disease.

Effects of a reduced oxygen tension culture system on human T cell clones as a function of in vitro age

2004 ◽  
Vol 39 (4) ◽  
pp. 525-530 ◽  
Author(s):  
Orla Duggan ◽  
Paul Hyland ◽  
Kathryn Annett ◽  
Robin Freeburn ◽  
Christopher Barnett ◽  
...  
Keyword(s):  
T Cell ◽  
Oxygen Tension ◽  
Culture System ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

539 Interleukin 4 (IL-4) is responsible for IgE synthesis induced in vitro by human T cell clones

1988 ◽  
Vol 81 (1) ◽  
pp. 303 ◽  
Author(s):  
S. Romagnani ◽  
G.F. Del Prete ◽  
E. Maggi ◽  
P. Parronchi ◽  
A. Tiri ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 4 ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones ◽  
Ige Synthesis

scholarly journals Rabies Virus-specific Human T Cell Clones Provide Help for an in vitro Antibody Response against Neutralizing Antibody-inducing Determinants of the Viral Glycoprotein

1989 ◽  
Vol 70 (6) ◽  
pp. 1513-1521 ◽  
Author(s):  
H. Bunschoten ◽  
R. J. Klapmuts ◽  
I. J. Th. M. Claassen ◽  
S. D. Reyneveld ◽  
A. D. M. E. Osterhaus ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Response ◽  
Rabies Virus ◽  
Neutralizing Antibody ◽  
Viral Glycoprotein ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

Interleukin-1 favours the in vitro development of type 2 T helper (Th2) human T-cell clones

1994 ◽  
Vol 145 (2) ◽  
pp. 93-100 ◽  
Author(s):  
R. Manetti ◽  
V. Barak ◽  
M.-P. Piccinni ◽  
S. Sampognaro ◽  
P. Parronchi ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 1 ◽  
T Helper ◽  
T Cell Clones ◽  
In Vitro Development ◽  
Human T Cell ◽  
Cell Clones ◽  
Vitro Development

Alloproliferative human T cell clones primed and cultured in vitro lose proliferative and gain suppressive activity with age

1984 ◽  
Vol 10 (2) ◽  
pp. 135-142 ◽  
Author(s):  
G. Pawelec ◽  
P. Wernet ◽  
A. Rehbein ◽  
I. Balko ◽  
E.M. Schneider
Keyword(s):  
T Cell ◽  
Suppressive Activity ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

scholarly journals Human T cell clones express functional homing receptors required for normal lymphocyte trafficking.

1985 ◽  
Vol 162 (3) ◽  
pp. 1075-1080 ◽  
Author(s):  
R F Navarro ◽  
S T Jalkanen ◽  
M Hsu ◽  
G Søenderstrup-Hansen ◽  
J Goronzy ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoid Tissues ◽  
Normal Lymphocyte ◽  
Lymphocyte Trafficking ◽  
High Endothelial Venules ◽  
T Cell Clones ◽  
Human T Cell ◽  
Cell Clones

To function efficiently in vivo, lymphocytes must circulate from the blood into lymphoid tissues and other sites of immune reaction. Herein, we show that human cytotoxic and helper T cell clones and lines, maintained in vitro with IL-2, express the functional capacity to recognize and bind to high endothelial venules (HEV), a capacity essential for lymphocyte exit from the blood, and hence for normal lymphocyte trafficking. The expression of functional homing receptors distinguishes human T cell clones from their murine counterparts, which uniformly lack receptors for HEV and are unable to migrate normally from the blood in vivo. The results raise the possibility that human T cell clones may be more effective in mediating in vivo immune responses than is suggested by murine models.

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