Biomedical Sciences Graduate Program | University of California, San Francisco

The work of my laboratory is focused on cellular immune responses to HIV, including: (1) The impact of HAART on HIV specific cellular immune responses, and (2) HIV transmission across mucosal barriers and the prevention of transmission through vaccination. Experimental questions in these areas are approached using preclinical systems that approximate the pathophysiology of HIV disease in vivo. The relevance of these systems and the conclusions drawn within them will be directly tested in studies of seropositive adults and children with HIV disease.

Many HIV infected subjects in the United States are treated with powerful combination antiretroviral drugs. These drugs reduce viral loads to low levels, but the removal of the antigenic drive also might reduce stimuli for HIV-specific immune responses. We are studying the differential impact of HAART on immune responses in patients treated early (who might have better preserved helper T cell responses and antigenic presentation networks) compared to those treated later in infection. As many patients stop drugs either on their own or in the context of structured therapeutic interruptions we study how the removal of drug affects the magnitude and breadth of HIV specific immunity. The latent viral reservoir is the major impediment to virus eradication. We seek to understand whether the virus in this reservoir is recognized by the immune system and aim to establish how immune responses may be targeted to this rare population of infected cells. We also study how T cells can be therapeutically manipulated using pharmacological agents to increase their potency.

The majority of HIV transmission occurs at a mucosal surface. Once virus crosses a mucosal barrier local innate immune responses are activated. We study Natural killer T (NKT) cells, rare T lymphocytes with immunoregulatory functions that recognize self and non-self glycolipids presented by CD1d molecules, and how they may affect HIV infection. We also investigate HIV specific immune responses at mucosal barriers, and how these contribute to the prevention of HIV transmission.

Selected Publications

Rose, NF, Marx PA, Luckay A, Nixon DF, Moretto WJ, Donahoe SM, Montefiori D, Roberts A, Buonocore L and Rose JK. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell, 2001 106:539-549.

Ortiz GM, Wellons M, Brancato J, Vo HTT, Zinn RL, Clarkson DE, Miralles GD, Van Loon K, Bonhoeffer S, Montefiori D, Bartlett JA and Nixon DF. Structured antiretroviral therapy interruption in chronically HIV-1-infected subjects. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13288-93.

Ortiz GM, Hu J, Goldwitz JA, Chandwani R, Larsson M, Bhardwaj N, Bonhoeffer S, Ramratnam B, Zhang L, Markowitz MM and Nixon DF. Residual viral replication during antiretroviral therapy boosts HIV-1-specific CD8+ T cell responses in subjects treated early after infection. J Virol. 2002 Jan;76(1):411-5.

Sandberg JK, Stoddart CA, Brilot F, Jordan KA, and Nixon DF. Development of innate CD4+ V24 NKT cells in the early human fetal thymus is regulated by IL-7. Proc. Natl. Acad. Sci. USA, 2004 101(18):7058-7063.

Schweighardt B, Roy AM, Meiklejohn DA, Grace EJ 2 nd, Moretto WJ, Heymann JJ, Nixon DF. R5 human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in primary CD4+ T-cell cultures than X4 HIV-1. J.Virology, 2004 17:9164-9173.

Moll M, Snyder-Cappione J, Spotts G, Hecht FM, Sandberg JK, Nixon DF. Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2. Blood, 2006 107(8):3081-3083.

Rakoff-Nahoum S, Kuebler PJ, Heymann JJ, Sheehy ME, Ortiz GM, Ogg GS, Barbour JD, Lenz J, Steinfeld AD, Nixon DF. Detection of T lymphocytes specific for human endogenous retrovirus K (HERV-K) in patients with seminoma. AIDS Research and Human Retroviruses, 2006 22(1):52-56. 5.

Michaëlsson J, Mold JE, McCune JM, Nixon DF. Regulation of T cell responses in the developing human fetus. J. Immunology, 2006 176(10):5741-5748.

information last updated August 2006