Antisense oligomers and methods for inducing immune tolerance and immunosuppression
First Claim
1. A method of inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10, comprising (a) exposing a population of human dendritic cells to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:
- 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
C., (b) by said forming, blocking expression of full-length CD86 in said cells, and (c) by said blocking, producing inhibition of the expression of full-length CD86 on the surface of dendritic cells, and enhanced expression of extracellular IL-10 by mature dendritic cells.
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Abstract
A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.
34 Citations
26 Claims
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1. A method of inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10, comprising
(a) exposing a population of human dendritic cells to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO: - 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
C.,(b) by said forming, blocking expression of full-length CD86 in said cells, and (c) by said blocking, producing inhibition of the expression of full-length CD86 on the surface of dendritic cells, and enhanced expression of extracellular IL-10 by mature dendritic cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
- 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
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20. A method of inducing mature human dendritic cells to a condition of increased production of extracellular IL-10, comprising
(a) exposing the population of cells containing mature dendritic cells to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD-86 transcript identified, in its processed form, by SEQ ID NO: - 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
C.,(b) by said forming, blocking expression of full-length CD86 in said cells, and (c) by said blocking, enhancing expression of extracellular IL-10 by the mature dendritic cells.
- 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
-
21. A composition for use in inducing dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10, said conjugate comprising,
a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD-86 transcript identified, in its processed form, by SEQ ID NO: - 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
C. - View Dependent Claims (22, 23, 25, 26)
- 33, to form a heteroduplex structure between said compound and transcript having a Tm of at least 45°
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24. The composition of claim 27, wherein X═
- NR2, where each R is independently hydrogen or methyl in the compound to which the T cells are exposed.
Specification