Precise T cell correlates of protection need to be identified for vaccine design

T cells are key players in the immune response to HIV, which are able to delete infected cells. This capacity is used for vaccine development against HIV. "To date however, success of this strategy remains elusive. Our understanding of T cell efficacy is still limited, and we need to identify precise T cell correlates of protection that could guide rationale vaccine design", says Victor Appay, Group leader HIV Pathogenesis and Immunosenescence, Hopital Pitie-Salpetriere, Paris, at the 2nd European Congress of Immunology ECI 2009 in Berlin.

T cell based vaccines against HIV focus on the subtype of CD8+ T cells, which are able to recognize and destroy virus infected cells and tumour cells. "Our aim is to return to basic Immunology to explore in details the factors that govern the development and maintenance of effective CD8+T cell responses in HIV infection" Appay stresses. For this purpose, the scientists use a variety of approaches based on novel technologies to study in HIV infected patients the functional attributes of CD8+ T cells down to the level of the primary immune resources.

The recent results highlight the importance of antigen sensitivity, i.e. the strength of 
interaction between the effector CD8+ cell and the HIV infected target cell to control HIV replication. Antigen sensitivity determines important features of CD8+ T cells: 1- the polyfunctional profile (i.e. the capacity to produce a number of effector soluble factors simultaneously), 2- the expansion and turnover (i.e. the celluar proliferation and replacement) 3- the HIV suppressive capacity of the T cells (i.e. the ability to maintain low levels of or even prevent HIV replication by killing infected cells), which are hallmarks of CD8+ T cell efficacy against HIV.

Moreover, the work of his team focuses also on the development with progressive HIV disease of premature immunosenescence, or immune ageing, a phenomenon which usually occurs in old age. "This work is directly relevant to strategies aimed at  developing successful T cell based vaccines and to our understanding  of HIV pathogenesis, but also more generally, of immune decline with  age" Appay says.