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 #: 1ZIAAI005031-10
• Application #: 8336384
• Support Year: 10
• Fiscal Year: 2011
• Total Cost: $154,483

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

Douek, Daniel C; Nabel, Gary J (2011) Vaccines. Immunol Rev 239:5-7

Sloand, Elaine M; Melenhorst, J Joseph; Tucker, Zachary C G et al. (2011) T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy. Blood 117:2691-9

Venturi, Vanessa; Quigley, Maire F; Greenaway, Hui Yee et al. (2011) A mechanism for TCR sharing between T cell subsets and individuals revealed by pyrosequencing. J Immunol 186:4285-94

Melenhorst, J Joseph; Scheinberg, Phillip; Williams, Ann et al. (2011) Alloreactivity across HLA barriers is mediated by both naïve and antigen-experienced T cells. Biol Blood Marrow Transplant 17:800-9

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