Eliminating graft-versus-host potential from T cell immunotherapeutic populations

Bone Marrow Transplant. 1996 Aug;18(2):415-20.

Abstract

It is common knowledge that donor T cells are responsible for graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), yet GVHD remains a grave threat to transplant patients. The donor marrow can be purged of T cells to reduce this danger, but the risks of viral infections, tumor relapse and graft rejection are then increased. Here we describe a method that may be used to provide BMT patients with T cell immunotherapeutic populations responsive to foreign antigens, but unresponsive to host HLA. The method involves the culture of donor T cells with host-derived B lymphoblastoid cell lines (BLCL). During culture, the T cells are activated by the mismatched host HLA. Activated cells are subsequently removed by fluorescence-activated cell sorting. Criteria for removal include cell size and the expression of multiple T cell activation antigens on cell membranes. After the procedure, T cell populations retain helper and cytotoxic T cell responses against foreign antigens, but are specifically devoid of responses to host HLA. This technique offers a promising method for providing BMT patients the benefits of T cell immunity without the consequences of GVHD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bone Marrow Transplantation / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Lymphocyte Activation
  • Lymphocyte Depletion*
  • T-Lymphocytes / immunology*