Methods for treating HIV infected subjects
First Claim
1. A method for selectively enriching a population of T cells in TH1 cells in vitro comprising:
- a) contacting a population of T cells with;
(1) an agent which provides a primary activation signal to the T cells thereby activating the T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof, an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation signal in the T cell when complexed with the TCR/CD3 complex; and
(2) an anti-CD28 antibody or a CD28-binding fragment thereof, thereby stimulating the activated T cells, such that the T cells are stimulated to proliferate and produce at least one TH1 cytokine, thereby selectively enriching the population of T cells in TH1 cells.
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Abstract
Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
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Citations
20 Claims
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1. A method for selectively enriching a population of T cells in TH1 cells in vitro comprising:
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a) contacting a population of T cells with;
(1) an agent which provides a primary activation signal to the T cells thereby activating the T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof, an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation signal in the T cell when complexed with the TCR/CD3 complex; and
(2) an anti-CD28 antibody or a CD28-binding fragment thereof, thereby stimulating the activated T cells, such that the T cells are stimulated to proliferate and produce at least one TH1 cytokine, thereby selectively enriching the population of T cells in TH1 cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
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9. A method for selectively enriching a population of T cells in TH2 cells in vitro comprising
a) contacting a population of T cells with: -
(1) an agent which provides a primary activation signal to the T cells thereby activating the T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof, an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation signal in the T cell when complexed with the TCR/CD3 complex; and
(2) a stimulatory form of a natural ligand of CD28 selected from the group consisting of B7-1, a CD28-binding fragment of B7-1, B7-2, and a CD28-binding fragment of B7-2, such that the T cells are stimulated to proliferate and produce at least one TH2 cytokine, thereby enriching the population of T cells in TH2 cells. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16)
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17. A method for increasing the proportion of TH1 versus TH2 cells in a population of T cells, comprising:
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a) contacting the population of T cells with;
(1) an agent which provides a primary activation signal to the T cells thereby activating the T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof, an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation signal in the T cell when complexed with the TCR/CD3 complex; and
(2) an anti-CD28 antibody or a CD28-binding fragment thereof, wherein the anti-CD28 antibody or a CD28-binding fragment is attached on a surface, thereby increasing the proportion of TH1 versus TH2 cells in the population of T cells compared to the proportion of TH1 versus TH2 cells in a population of T cells not contacted with an agent which provides a primary activation signal to the T cells and an anti-CD28 antibody or a CD28-binding fragment thereof. - View Dependent Claims (18, 19, 20)
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Specification