The role of Regulatory T cells in the pathogenesis of HIV-2 infection

Lead Research Organisation: MRC Unit, The Gambia

Abstract

The worldwide AIDS pandemic is largely caused by a virus that occurs in two strains. One HIV strain called HIV-1, which after a variable length of time leads to AIDS and death in most infected people. There is a second HIV strain called HIV-2, which is mostly found in West Africa. This virus behaves quite differently from HIV-1: some HIV-2-infeceted people develop AIDS just as if they had HIV-1 but others, as many as 80%, have a normal lifespan and die of old age instead.||Special (regulatory) cells in the immune system may play a critical role in fighting the disease. There is a need to elucidate if these cells play a protective role that would assist the development of an HIV vaccine. We postulate that in certain infected subjects the physiological balance between different cells in the immune system is maintained whereas in other infected patients this is not the case. In the first instance we will evaluate the numbers and function of these cells in a cross-sectional study of infected individuals and then characterize the cells.

Technical Summary

A virus-specific CD8+ T lymphocyte response early in the course of viral infections is essential for the successful control of viral replication, and a maintained response is needed for continued viral control. However, HIV infection is characterized by an aberrant immune activation and paradoxically immune suppression also occurs from early infection. Ultimately HIV causes progressive immune dysfunction and death. The majority of HIV-2 infected individuals have low or undetectable viral load and are regarded as Long-term non-progressors (LTNP). T regulatory cells (T reg) are a subset of CD4+ T cells with immunosuppressive properties and these cells may play a critical role in counteracting immunopathology resulting from persistent high level of immune stimulation from chronic viral infections. There is a need to elucidate if T regs play a protective role by dampening immune activation or have a role in accentuating infection by suppressing immune control. An understanding of the balance between T reg and effector T cell functions in HIV-2 infection would greatly assist the development of an HIV vaccine. We postulate that in HIV-2 subjects with a normal CD4 count and a low viral load (LTNPs) the physiological balance between regulatory T cell activity and T cell activation is maintained whereas in both HIV-1 or HIV-2 patients with progressive disease and a high viral load this is not the case. In the first instance we will evaluate the numbers and function of regulatory T-cells in a cross-sectional study of HIV-1 and HIV-2 individuals with high CD4 T cell count and then characterize both Tregs and effector T cell phenotypes in HIV-2 LTNPs.

Publications

10 25 50
 
Description MRC Open-Days for Public Visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Poster presentations and demonstrations of research output. Discussions on relationships with patients and the public.

It changed the perception of the general public about MRC research activities and has strengthened the relationship betweem MRC and the public and Government of the Gambia
Year(s) Of Engagement Activity 2006