Understanding the basis of antigen-presenting cell and T cell dysfunction in HIV infection is critical for the rational design of immunotherapies and prophylactic and therapeutic vaccines.

An increasing body of evidence indicates that HIV infection is associated with extreme and persistent immune activation, and recent studies have shown that parameters of systemic immune activation correspond to and are predictive of clinical HIV disease progression. Deciphering the components that contribute to this immune activation process, and identifying immunoregulatory mechanisms that protect the host against HIV-associated immune overstimulation are therefore critical for the understanding of HIV immunopathogenesis.

However, other important studies have shown that T cell impairment occurring in chronic infections, including HIV, is at least in part under control of inhibitory mechanisms that may be reverted by manipulation of regulatory pathways. These findings are important for our understanding of HIV pathogenesis as well as for the potential development of novel immunotherapeutic strategies.

Blockade of some of these immunoregulatory networks has been shown to restore T cell function and enhance antigen clearance both in animal models of chronic viral infections and in tumors, including metastatic cancer in humans. The combination of continuous global immune activation and upregulation of inhibitory pathways in virus-specific cells raises therefore specific challenges in HIV infection.

Determining how antigen-presenting cells, in particular dendritic cells, facilitate the formation of an effective HIV-specific adaptive immune response while minimizing bystander immune overactivation is an important step in identifying components of protective immunity against HIV infection.

In addition, identifying crucial defects that selectively inhibit virus-specific lymphocyte subsets may provide additional therapeutic targets for adjuvants of future preventive or therapeutic vaccines. 

Laboratories which focus on Immune Activation:
		Altfeld Lab
		Kaufmann Lab
		Walker Lab
		Yu Lab