Eliminating graft-versus-host potential from T cell immunotherapeutic populations.
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.
Rencher
S D
SD
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38101, USA.
Houston
J A
JA
Lockey
T D
TD
Hurwitz
J L
JL
D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000276:immunology*