Respiratory syncytial virus renders dendritic cells tolerogenic
AssigneeBaylor Research Institute
InventorsJOHN E. CONNOLLY, JACQUES F. BANCHEREAU, MICHELLE A. GILL
Life of this patent
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Abstract
The present invention includes compositions, methods and systems for inducing immune tolerance using antigen presenting cells by infecting isolated antigen presenting cells with an effective amount of respiratory syncytial virus (RSV) or portions thereof sufficient to infect the antigen presenting cells and contacting CD4+, CD8+ or both CD4+ T cells and CD8+ T cells with the RSV-infected antigen presenting cells, wherein the CD4+, CD8+ or both CD4 and CD8+ T cells are rendered tolerogenic as measured in vitro by a mixed leukocyte reaction.
Claims23
A method for inducing immune tolerance using antigen presenting cells comprising;
- infecting isolated antigen presenting cells with an effective amount of respiratory syncytial virus (RSV) or portions thereof sufficient to infect the antigen presenting cells;
- and
- contacting CD4+, CD8+ or both CD4+ T cells and CD8+ T cells with the RSV-infected antigen presenting cells, wherein the CD4+, CD8+ or both CD4 and CD8+ T cells are rendered tolerogenic as measured in vitro by a mixed leukocyte reaction.
A method for making tolerizing dendritic cells comprising;
- infecting dendritic cells with effective amount of respiratory syncytial virus to develop IL-10 dependent tolerogenic immune function, wherein respiratory syncytial virus increased the dendritic cells' ability to tolerize allogeneic CD4+ T-cells, cause suppressor T-cell proliferation, secrete IL-10 and express inhibitory molecules PDL-1, ILT-4 and HLA-G and wherein the infecting dendritic cells are CD80high, CD86high, CD40high and CD83low.
A method for suppressing antiviral immunity of dendritic cells in a subject comprising;
- infecting isolated dendritic cells with effective amount of respiratory syncytial virus to develop IL-10 dependent tolerogenic immune function, wherein respiratory syncytial virus inhibit the dendritic cells' ability to activate allogeneic CD4+ T-cells, induce naïve T-cell regulatory response, secrete IL-10 and express inhibitory molecules PDL-1, IKT-4, and HLA-G when reintroduced into a patient.
A tolerogenic dendritic cell comprising an isolated dendritic cells that is CD80high, CD86high, CD40high and CD83low.
A tolerogenic dendritic cell made by the method of infecting peripheral blood mononuclear cells with an effective amount of a respiratory syncytial virus or portions thereof sufficient to rendered CD4+, CD8+ or both CD4+ T cells and CD8+ T cells tolerogenic as measured in vitro by a mixed leukocyte reaction and wherein the dendritic cells that is CD80high, CD86high, CD40high and CD83low.
A method of promoting tolerogenic T cell-mediated immune responses by contacting the T cells with a dendritic cell that has been infected with an amount of a RSV or portion thereof sufficient to trigger the surface expression of at least one of CD80high, CD86high, CD40high and CD83low.
A method of inducing anergic T helper cells which comprises:
- incubating isolated antigen presenting cells (APC) with an amount of RSV sufficient to infect the antigen presenting cell and trigger the surface expression of at least one of the following cell surface markers CD80high, CD86high, CD40high and CD83low;
- and
- contacting the RSV-infected antigen presenting cells with T cells under conditions that tolerize the T cells as measured in vitro in a mixed lymphocyte reaction.
A method of producing an isolated tolerogenic dendritic cell comprising:
- incubating the isolated dendritic cell with an amount of respiratory syncytial virus sufficient to infect the dendritic cell under conditions that trigger the cell surface expression the following cell surface CD80high, CD86high, CD40high and CD83low.
A kit for enhancing tolerogenicity in a mammalian host comprising isolated tolerogenic dendritic cells previously infected with RSV and having the following cell surface CD80high, CD86high, CD40high and CD83low.
A method of generating a tolerogenic antigen presenting cell (APC) comprising:
- infecting the APC with an amount of respiratory syncytial virus sufficient to infect the dendritic cell;
- and
- causing the following cell surface marker expression CD80high, CD86high, CD40high and CD83low thereby generating a tolerogenic antigen presenting cell (APC).
A method for treating an autoimmune disease in a mammalian subject, comprising administering to the mammalian subject tolerogenic antigen presenting cell (APC), wherein the tolerogenic dendritic cells previously infected with RSV and having the following cell surface CD80high, CD86high, CD40high and CD83low, and the cells are administered in an amount effective to reduce or eliminate the autoimmune disease or to prevent its occurrence or recurrence.
A method for modulating the immune response to an antigen, comprising administering to a patient in need of such treatment an isolated tolerizing antigen-presenting cell for a time and under conditions sufficient to modulate the immune response, wherein the antigen-specific antigen-presenting cell is produced by contacting the antigen-presenting cell with RSV for a time and under conditions sufficient for the antigen-presenting cell to become a tolerizing to T cells, wherein the tolerizing antigen-presenting cell is characterized by expressing the following cell surface markers CD80high, CD86high, CD40high and CD83low, and wherein the tolerizing antigen presenting cell is tolerogenic at a ratio of 1:5 to 1:100 tolerizing antigen presenting cells to T cells.
Dependencies are inferred from the claim text.