Human dendritic cells transfected with amplified MUC1 mRNA stimulate cytotoxic T lymphocyte responses against pancreatic cancer in vitro

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.

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In vitro effects of malathion and O,O,S-trimethyl phosphorothioate on cytotoxic T-lymphocyte responses

Pesticide Biochemistry and Physiology ◽

10.1016/0048-3575(85)90136-1 ◽

1985 ◽

Vol 24 (2) ◽

pp. 260-266 ◽

Cited By ~ 22

Author(s):

Kathleen E. Rodgers ◽

Marcia H. Grayson ◽

Toshiko Imamura ◽

Bruce H. Devens

Keyword(s):

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

In Vitro Effects ◽

Lymphocyte Responses

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Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro.

Journal of Experimental Medicine ◽

10.1084/jem.175.2.609 ◽

1992 ◽

Vol 175 (2) ◽

pp. 609-612 ◽

Cited By ~ 130

Author(s):

S Nair ◽

F Zhou ◽

R Reddy ◽

L Huang ◽

B T Rouse

Keyword(s):

Dendritic Cells ◽

T Lymphocyte ◽

Antigen Processing ◽

Vaccine Development ◽

Cytotoxic T Lymphocyte ◽

Present Report ◽

Soluble Proteins ◽

Ph Sensitive ◽

Ctl Response

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.

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Residual Lymphocytes in GM-CSF and IL-15 Differentiated Monocyte-Derived Dendritic Cells Enables Cytotoxic T Lymphocyte Responses.

Blood ◽

10.1182/blood.v110.11.4907.4907 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4907-4907

Author(s):

Melinda Y. Hardy ◽

Andrew J. Kassianos ◽

Ray Wilkinson ◽

Annelie Vulink ◽

Derek N.J. Hart ◽

...

Keyword(s):

Dendritic Cells ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Small Population ◽

Lymphoid Cells ◽

Gm Csf ◽

Hla Dr ◽

Ifn Γ ◽

Human Dendritic Cells ◽

Ctl Responses

Abstract We investigated the capacity of IL-15 to differentiate human dendritic cells (DC) from monocytes in the presence of GM-CSF (IL-15 MoDC) and compared them with MoDC differentiated in IL-4 and GM-CSF (IL-4 MoDC) as used in many immunotherapy protocols. IL-15 MoDC expressed higher levels of CD40 and HLA-DR and importantly, induced MART-1 specific cytotoxic T lymphocyte (CTL) responses with superior lytic capacity, when compared to IL-4 MoDC. In response to activation, IL-15 MoDC secreted high levels of IFN-γbut low or no IL-12, whereas IL-4 MoDC secreted high IL-12 but low or no IFN-γ. Using an IFN-γ blocking antibody, we demonstrated that IFN-γ production by the IL-15 MoDC did not account for the superior CTL responses induced. Despite immunoselecting monocytes to greater than 97% purity prior to DC differentiation, we noticed a small population (1–2%) of CD56+ and CD3+ lymphocytes in the IL-15 MoDC preparations that were less prominent in IL-4 MoDC differentiated from the same monocytes. Removal of the residual lymphocytes from monocytes prior to differentiation into IL-15 MoDC diminished their capacity to induce CTL but did not affect the expression of HLA-DR or CD40. These data suggest that IL-15-dependent cross-talk between the small lymphoid populations present and DC, during DC differentiation from monocytes results in superior CTL priming that is independent of IL-12 and IFN-γ. Based on these results, appropriately manufactured IL-15 MoDC preparations containing defined numbers of lymphoid cells should be considered for immunotherapy.

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