HIV-1 preferentially infects CD4+ T helper cells, which play a crucial role in the orchestration of the immune system. The main function of CD4+ T helper cells is to direct and focus immune responses to maximize anti-pathogenic processes, while suppressing non-essential immune responses. In particular, the efficiency of CD4+ T cell help has been strongly associated with the efficacy of virus-specific CD8+ T cell function. Understanding exactly how CD4+ T helper cells coordinate the immune system and respond to immune challenges are likely crucial to the development of an effective HIV vaccine.
Approaches to induce HIV-1-specific CD4+ T cell responses have been met with skepticism thus far as these attempts may expand the pool of HIV-1 specific CD4+ T cells targets.
New studies from our laboratory demonstrate that HIV-1-specific CD4+ T helper responses are able to critically improve HIV-1-specific CD8+ T cells in their functionality but also to successfully inhibit viral replication. These responses are enriched in subjects, who are able to control viral replication and resurrected through antiretroviral therapy.
Our studies are performed in the context of both acute and chronic HIV-1 infection. We therefore examine different group of patients from highly viremic rapid progressors to HIV elite controllers and we also investigate the impact of genetic factors and antiretroviral therapy on HIV-1-specific CD4+ responses.
Much of this work is technically challenging, and requires the creative use of innovative techniques and new technologies.
| Present Areas of Investigation: | ||
| Studying CD4 signaling help necessary for inhibition of viral replication by HIV-1 specific CD8+ T cells | ||
| Characterizing CD4 help for specific B-cell responses | ||
| Investigating prospective cytolytic CD4 activity in HIV-1 infection | ||
| Assessing the role of HIV-1-specific CD4+ T cells in the gastrointestinal tract | ||
| Identifying mechanisms which lead to the observed patterns of immunodominance of T cell responses in acute HIV-1 infection | ||