Immune Reconstitution

Douek, Daniel Cesar

Abstract

In patients treated with chemotherapy and bone marrow transplantation for leukemia, there are variable rates of reconstitution of T cell numbers and function. An understanding of the mechanisms underlying the recovery of T cells will be important for the design of future strategies to improve T cell reconstitution. The thymus is the organ responsible for producing new naive T cells with a broad immune repertoire from bone marrow-derived precursors. This study examines the role of the thymus in immune reconstitution and how it is affected by immunosuppression and graft-versus-host disease. We also pursue the same therapeutic goals in HIV-infected individuals aiming to improve immune reconstitution.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI005031-06
• Application #: 7592401
• Support Year: 6
• Fiscal Year: 2007
• Total Cost: $339,289

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Rezvani, Katayoun; Yong, Agnes S M; Savani, Bipin N et al. (2007) Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood 110:1924-32

Rezvani, K; Price, D A; Brenchley, J M et al. (2007) Transfer of PR1-specific T-cell clones from donor to recipient by stem cell transplantation and association with GvL activity. Cytotherapy 9:245-51

Scheinberg, Phillip; Melenhorst, Jan J; Hill, Brenna J et al. (2007) The clonal composition of human CD4+CD25+Foxp3+ cells determined by a comprehensive DNA-based multiplex PCR for TCRB gene rearrangements. J Immunol Methods 321:107-20

Seggewiss, Ruth; Lore, Karin; Guenaga, F Javier et al. (2007) Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood 110:441-9

Scheinberg, Phillip; Price, David A; Ambrozak, David R et al. (2006) Alloreactive T cell clonotype recruitment in a mixed lymphocyte reaction: implications for graft engineering. Exp Hematol 34:788-95

Lore, Karin; Seggewiss, Ruth; Guenaga, F Javier et al. (2006) In vitro culture during retroviral transduction improves thymic repopulation and output after total body irradiation and autologous peripheral blood progenitor cell transplantation in rhesus macaques. Stem Cells 24:1539-48

Takase, Hiroshi; Yu, Cheng-Rong; Mahdi, Rashid M et al. (2005) Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals. Int Immunol 17:1131-40

Laugel, Bruno; Boulter, Jonathan M; Lissin, Nikolai et al. (2005) Design of soluble recombinant T cell receptors for antigen targeting and T cell inhibition. J Biol Chem 280:1882-92

Muraro, Paolo A; Douek, Daniel C; Packer, Amy et al. (2005) Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med 201:805-16

Fujiwara, Hiroshi; Melenhorst, J Joseph; El Ouriaghli, Frank et al. (2005) In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40 ligand-activated B cells gene modified to express primary granule proteins. Clin Cancer Res 11:4495-503