1 post-doctoral fellow, 1 research technician

Dr Kaufmann’s research interest focuses on the role that immunoregulatory networks play in HIV-specific T cell dysfunction. The main purpose of his research efforts is to identify mechanisms that mediate a reversible impairment of T cell responses in HIV-infected individuals, which will further our understanding of HIV immunopathogenesis and could provide new targets for immunomodulatory therapies. The laboratory has the following major areas of interest. 1) The analysis of the role that the B7/CD28 family of co-signaling molecules plays in HIV-specific CD4 and CD8 T cell dysfunction. 2) The study of the role that these co-signaling molecules play in the gut-associated lymphoid tissue (GALT) compared to peripheral blood. 3) By comparing subjects with progressive HIV disease to people who spontaneously control the virus in the absence of therapy (“elite controllers”), we are analyzing the differences between functional T cell responses and ineffective, “exhausted” T cell responses, focusing in particular on inhibitory pathways. 4) Lastly, we are collaborating with study sites in Peru, Thailand and China in order to study HIV-CD4 T cell specificities and epitope cross-reactivity in individuals of various ethnic backgrounds infected by different viral clades.

Important Past Accomplishments:

• Study of dissociated CD4- viral load responses in HIV-infected individuals who remain viremic on antiviral therapy (HAART).
• Detailed comprehensive analysis of HIV-specific CD4 T cell responses at the single peptide level.
• Demonstration that treatment of acute HIV infection followed by supervised treatment interruptions does not lead to long-lasting control of viremia in the majority of subjects
• Demonstration of the involvement of the PD-1 pathway in HIV-specific T cell dysfunction.
• Analysis of the selective involvement of the CTLA-4 pathway in HIV-specific CD4 T cell dysfunction.

• Analysis of the role of the B7/CD28 family of co-signaling molecules, in particular PD-1 and CTLA-4, in HIV-specific CD4 and CD8 T cell dysfunction.
• Study that the role that the B7/CD28 family of co-signaling molecules plays in the gut-associated lymphoid tissue (GALT) compared to peripheral blood.
• Analysis of the qualitative differences between T cell responses in progressive HIV infection and T cell responses in subjects who control viral load in the absence of therapy (“elite controllers”), in particular with regard to inhibitory pathways.

Publications of Interest:

1. Kaufmann DE*, Kavanagh DG*, Pereyra F John J. Zaunders JJ, Mackey EW, Miura T, Palmer S, Brockman M, Rathod A, Piechocka-Trocha A, Baker B, Zhu B, Legall S, Waring MT, Ahern R, Moss K, Kelleher AD, Coffin JM, Freeman GJ, Rosenberg ES and Walker BD. CTLA-4 upregulation in HIV-specific CD4 T cells correlates with disease progression and defines a reversible immune dysfunction. Nature Immunology 2007, Sep 30. [Epub ahead of print] (*first co-authors).
   
2. Day CL*, Kaufmann DE*, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ and Walker BD. PD-1 expression on HIV-specific T cells is associated with T cell exhaustion and disease progression. Nature 2006; 443:350-54. (*first co-authors)
3. Kavanagh DG*, Kaufmann DE*, Sunderji S, Wagner BS, LeGall S, Boczkowski D, Rosenberg ES, Gilboa E, Walker BD, and Bhardwaj N. Dendritic cells isolated from HIV-1 infected patients and transfected with mRNA encoding lysosome-targeted antigen expand autologous antiviral CD4+ and CD8+ T cells with broad specificity and high proliferative capacity. Blood. 2006; 107(5):1963-9. Epub 2005 Oct 25 (*first co-authors)
4. Kaufmann DE*, Lichterfeld M*, Altfeld M, Addo MM, Johnston MN, Lee PK, Wagner BS, Kalife E, Strick D, Rosenberg ES and Walker BD. Limited Durability of Viral Control Following Treated Acute HIV Infection. PLoS Medicine 2004; 1:e36 (*first co-authors)
5. Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, Cosimi LA, Addo MM, Lichterfeld M, Altfeld M, Frahm N, Brander C, Sette A, Walker BD, Rosenberg ES. Comprehensive Analysis of HIV-1-Specific CD4 Responses Reveals Marked Immunodominance of Gag and Nef and the Presence of Broadly Recognized Peptides. J Virol 2004; 78:4463-4477.

Additional Information

For additional information contact:
Daniel E. Kaufmann, M.D.
Instructor in Medicine
Partners AIDS Research Center
Massachusetts General Hospital
Harvard Medical School
Bldg. 149, 13th Street, Rm 6618B
Charlestown, MA 02129
Phone 617 726-8630
Fax 617 726-5411
dkaufmann@partners.org