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: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI005031-08
• Application #: 7964835
• Support Year: 8
• Fiscal Year: 2009
• Total Cost: $550,000

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Chinn, I K; Milner, J D; Scheinberg, P et al. (2013) Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly. Clin Exp Immunol 173:140-9

Ombrello, Michael J; Remmers, Elaine F; Sun, Guangping et al. (2012) Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med 366:330-8

Melenhorst, Jan Joseph; Tian, Xin; Xu, Dihua et al. (2012) Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation. Haematologica 97:867-73

Koup, Richard A; Graham, Barney S; Douek, Daniel C (2011) The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors. Nat Rev Immunol 11:65-70

Rotger, Margalida; Dalmau, Judith; Rauch, Andri et al. (2011) Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. J Clin Invest 121:2391-400

Hippen, Keli L; Merkel, Sarah C; Schirm, Dawn K et al. (2011) Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity. Sci Transl Med 3:83ra41

van Bockel, David J; Price, David A; Munier, Mee Ling et al. (2011) Persistent survival of prevalent clonotypes within an immunodominant HIV gag-specific CD8+ T cell response. J Immunol 186:359-71

Sandler, Netanya G; Koh, Christopher; Roque, Annelys et al. (2011) Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 141:1220-30, 1230.e1-3

Haney, Danielle; Quigley, Máire F; Asher, Tedi E et al. (2011) Isolation of viable antigen-specific CD8+ T cells based on membrane-bound tumor necrosis factor (TNF)-? expression. J Immunol Methods 369:33-41

Miles, John J; Douek, Daniel C; Price, David A (2011) Bias in the ?? T-cell repertoire: implications for disease pathogenesis and vaccination. Immunol Cell Biol 89:375-87