KINETIC ANALYSIS OF CLONED CYTOTOXIC T LYMPHOCYTE REACTIVITY AGAINST NORMAL AND LEUKAEMIC TARGET CELLS

1986 ◽  
Vol 13 (2-3) ◽  
pp. 275-286 ◽  
Author(s):  
A. V. Lefever ◽  
R. L. Truitt
1988 ◽  
Vol 91 (2) ◽  
pp. 179-189 ◽  
Author(s):  
K.L. Sung ◽  
L.A. Sung ◽  
M. Crimmins ◽  
S.J. Burakoff ◽  
S. Chien

The biophysical properties of cytotoxic T lymphocytes during the killing of their target cells was investigated by using a human cytotoxic T lymphocyte clone, F1, and the target cell, JY, for which it is specific. In single cytotoxic cell/target cell pairs after their conjugation there are changes in the viscoelastic properties of the target cell in association with the lethal hit delivery and post-binding cytolytic steps. On the basis of these changes in the target cell, the complex cytolytic event can be divided into stages: the viscoelastic coefficients exhibited an initial increase followed by a return to resting values; thereafter these coefficients decreased below control and then rose again prior to lysis. The eventual killing of the target cell involves bubbling and swelling of the nucleus, clustering of granules, damage to the cytoplasmic membrane, cell swelling, and lysis. The viscoelastic changes involved in target cell death suggest the loss of integrity of its cytoskeletal apparatus.


1980 ◽  
Vol 152 (6) ◽  
pp. 1805-1810 ◽  
Author(s):  
J P Lake ◽  
M E Andrew ◽  
C W Pierce ◽  
T J Braciale

The in vitro secondary cytotoxic T lymphocyte (CTL) response to Sendai virus-treated stimulator cells by primed spleen cells from thymus gland-grafted nude mice was examined. BALB/c (H-2d) nude mice grafted with allogeneic C57BL/10 (H-2b) thymus glands developed CTL responses directed exclusively to Sendai virus-infected H-2d target cells. (C57BL/6 X BALB/c)F1 nude mice grafted with thymus glands of either parent developed CTL responses preferentially against infected target cells expressing the MHC antigens present in the parental thymus graft, but also had detectable activity for infected target cells of the parental haplotype not expressed in the thymus. These results provide evidence against the concept that self recognition by MHC-restricted CTL is directed exclusively by the MCH type of the thymus.


2000 ◽  
Vol 74 (12) ◽  
pp. 5470-5476 ◽  
Author(s):  
Arièle Azoulay-Cayla ◽  
Sven Dethlefs ◽  
Béatrice Pérarnau ◽  
Eva-Lotta Larsson-Sciard ◽  
François A. Lemonnier ◽  
...  

ABSTRACT H-2b mice are resistant to persistent infection of the central nervous system by Theiler's virus. They clear the infection 7 to 10 days after intracranial inoculation. Resistance maps to the H-2D gene and not to the H-2K gene and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) response. We used H-2b mice in which theH-2D or the H-2K gene had been inactivated to dissect the respective roles of these genes in resistance. We report that H-2D −/− but notH-2K −/− mice were susceptible to persistent infection. Furthermore, whereas H-2K −/−mice mounted a vigorous virus-specific CTL response, similar to that of control C57BL/6 mice, the CTL response ofH-2D −/− mice was nil or minimal. Using target cells transfected with the H-2Db or theH-2Kb gene, we showed that theH-2K-restricted CTL response against the virus was minimal in H-2D −/− mice. These results demonstrate that the H-2Db andH-2Kb genes play nonredundant roles in the resistance to this persistent infection.


1988 ◽  
Vol 69 (5) ◽  
pp. 751-759 ◽  
Author(s):  
Shin-Ichi Miyatake ◽  
Haruhiko Kikuchi ◽  
Kohichi Iwasaki ◽  
Junkoh Yamashita ◽  
Yuzirou Namba ◽  
...  

✓ Eleven lymphocyte clones were established from the peripheral blood lymphocytes of a patient with gliosarcoma by means of autologous tumor stimulation and the limiting-dilution technique with recombinant interleukin-2. Ten of the 11 clones were cytotoxic against the autologous tumor cell line GI-1. Seven of the 10 clones were also cytotoxic against allogeneic brain-tumor lines and HeLa cells, one clone was cytotoxic against several target cells, and two clones were specifically cytotoxic against GI-1 and allogeneic brain-tumor cells. One of the 11 clones was not cytotoxic against any target cells tested. Lymphokine-activated killer cells induced by recombinant interleukin-2 alone exhibited cytotoxic activity against all target tumor cells tested. Surface phenotypic analysis revealed that all lymphocyte clones expressed CD3 antigen, some expressed CD4 antigen, and others expressed CD8 antigen. These clones seemed to be antigen-specific cytotoxic T lymphocyte clones. Analysis with these antigen-specific cytotoxic T lymphocyte clones may be useful in the elucidation of tumor-specific or tumor-associated antigens on autologous tumor cells.


2014 ◽  
Vol 106 (8) ◽  
pp. 1780-1791 ◽  
Author(s):  
Saikrishna Gadhamsetty ◽  
Athanasius F.M. Marée ◽  
Joost B. Beltman ◽  
Rob J. de Boer

2001 ◽  
Vol 75 (14) ◽  
pp. 6273-6278 ◽  
Author(s):  
Michael B. A. Oldstone ◽  
Hanna Lewicki ◽  
Dirk Homann ◽  
Christophe Nguyen ◽  
Sylvianne Julien ◽  
...  

ABSTRACT Members of the Arenaviridae family have been isolated from mammalian hosts in disparate geographic locations, leading to their grouping as Old World types (i.e., lymphocytic choriomeningitis virus [LCMV], Lassa fever virus [LFV], Mopeia virus, and Mobala virus) and New World types (i.e., Junin, Machupo, Tacaribe, and Sabia viruses) (C. J. Peters, M. J. Buchmeier, P. E. Rollin, and T. G. Ksiazek, p. 1521–1551, in B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996; P. J. Southern, p. 1505–1519, in B. N. Fields, D. M. Knipe, and P. M. Howley [ed.], Fields virology, 3rd ed., 1996). Several types in both groups—LFV, Junin, Machupo, and Sabia viruses—cause severe and often lethal human diseases. By sequence comparison, we noted that eight Old World and New World arenaviruses share several amino acids with the nucleoprotein (NP) that consists of amino acids (aa) 118 to 126 (NP 118–126) (RPQASGVYM) of LCMV that comprise the immunodominant cytotoxic T-lymphocyte (CTL) epitope forH-2 d mice (32). This Ld-restricted epitope constituted >97% of the total bulk CTLs produced in the specific antiviral or clonal responses ofH-2 d BALB mice. NP 118–126 of the Old World arenaviruses LFV, Mopeia virus, and LCMV and the New World arenavirus Sabia virus bound at high affinity to Ld. The primary H-2 d CTL anti-LCMV response as well as that of a CTL clone responsive to LCMV NP 118–126 recognized target cells coated with NP 118–126 peptides derived from LCMV, LFV, and Mopeia virus but not Sabia virus, indicating that a common functional NP epitope exists among Old World arenaviruses. Use of site-specific amino acid exchanges in the NP CTL epitope among these arenaviruses identified amino acids involved in major histocompatibility complex binding and CTL recognition.


1985 ◽  
Vol 63 (5) ◽  
pp. 763-770 ◽  
Author(s):  
Toshiki Yamasaki ◽  
Hajime Handa ◽  
Junkoh Yamashita ◽  
Yoshihiko Watanabe ◽  
Masaaki Taguchi ◽  
...  

✓ The authors have established a murine malignant glioma-specific cytotoxic T lymphocyte clone (G-CTLL 1) by T cell growth factor (TCGF) using 203-glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin). The cloned cells were found to release a large amount of gamma interferon (IFN) in response to glioma-associated antigen-specific stimulation. The authors have investigated whether the IFN produced can contribute to killing the target cells. Adding anti-mouse gamma IFN antibody to the mixed clone-target cell culture inhibited IFN production by the cloned cells but the toxicity of the cells was minimally diminished. Therefore, it is suggested that the endogenous gamma IFN produced by the TCGF-dependent cloned cytotoxic T lymphocyte line does not have direct cytotoxic action on the target cells. Furthermore, IFN production as well as cytotoxicity was blocked by anti-Lyt-2 monoclonal antibody in the absence of complement. This suggests that IFN plays a role in the process of antigen recognition of target cells because the Lyt-2 molecule is involved in an antigen-specific function on the cytotoxic T lymphocyte receptor. The role of TCGF in gamma IFN production was also investigated. The spontaneous production of gamma IFN by the cloned cells paralleled the amounts of exogenous TCGF added to the cultures, but TCGF had no synergistic effect on IFN production in the presence of mitogen or tumor antigen. Accordingly, it is possible that TCGF stimulates the cloned cells to proliferate, causing IFN release.


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