Methods for eliminating at least a substantial portion of a clonal antigen-specific memory T cell subpopulation
View Patent ↗The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.
1. A method for eliminating at least a substantial portion of a clonal antigen-specific memory T cell subpopulation from a mixed population of T cells from an individual, comprising,
exposing a population of cells comprising the mixed population of T cells to a surface,
said exposure comprising contacting said population of cells with said surface at a ratio of surface to cells of at least 5:1, wherein the surface has attached thereto an anti-CD3 antibody and an anti-CD28 antibody, or antigen-binding fragments thereof; and wherein said exposure results in apoptosis or growth inhibition in at least a substantial portion of at least one clonal antigen-specific memory T cell population present in the mixed population of T cells without requiring further activation or stimulation;
thereby eliminating at least a substantial portion of said clonal antigen-specific memory T cell population from the mixed population of T cells.
2. The method of claim 1 further comprising expanding the remaining mixed population of T cells.
3. The method of claim 2 wherein the remaining mixed population of cells is expanded by further exposing the remaining mixed population of cells to the surface; wherein the ratio of surface to cells is from about 1:1 to about 1:10, thereby stimulating and expanding said remaining T cells.
4. The method of claim 3 wherein the exposure of said cells to said surface is for a time sufficient to increase polyclonality.
5. The method of claim 4 wherein the increase comprises a shift from mono to oligoclonality or to polyclonality of the T cell population as measured by a Vβ, Vα, Vγ, or Vδ spectratype profile of at least one Vβ, Vα, Vγ, or Vδ family gene.
6. The method of claim 1 or claim 3 wherein the surface is a paramagnetic bead.