The role of T cell immunity in HIV-1 infection

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Highlights

  • •

    Responses to structurally constrained regions of HIV-1 are most effective in reducing viral replication.

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    The quality of the T cell response is important; polyfunctionality, balance of Treg vs Th17 and infection of TFH.

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    T cell responses in studies of controllers and progressors are instructive for future development of therapies and vaccines.

The interplay between the T cell immune response and human immunodeficiency virus (HIV)-1 largely determines the outcome of infection. Typically, the virus overcomes the immune defences leading to a gradual decline in function that permits the development of disease. In recent years, a concerted effort in comparing T cell responses between ‘controllers’ and ‘progressors’ is beginning to identify the T cell subsets and factors that affect disease progression related to the effector functions of both CD4 and CD8 T cells. These efforts are providing opportunities for development of novel therapies and vaccines.

Introduction

HIV-1 primarily infects and destroys CD4 T cells and causes dysfunction of most T cell subsets, presenting a formidable challenge to the immune system. A high rate of replication causes rapid, disseminated infection of CD4 T cells in the first few weeks and a sizeable reduction in CD4 T cell numbers. Over the long term, CD4 T cell death outnumbers the thymic output of new cells, resulting in a progressive depletion. In addition, a subset of resting memory CD4 T cells harbour latent HIV-1 DNA that cannot be cleared and are largely unaffected by drug therapies. Therefore, once established, HIV infection is life-long. This article reviews CD4 and CD8 T cell immunity to HIV-1, focusing on recent progress in the field.

Section snippets

The non-protective T cell response to HIV-1

The vast majority of individuals are ultimately susceptible to HIV disease. Robust neutralising antibody responses develop too slowly to control infection and although the T cell response is comparatively quicker, viral loads in excess of 106 copies/mL of plasma are often reached during acute infection before T cell-mediated inhibition of infected cells reduces the viral load to a typical steady-state level of ∼3 × 104 copies/mL [1, 2]. There are a number of factors that contribute to the failure

HLA Class I

Spontaneous resolution of HIV infection does not occur and therefore there is no natural immune correlate for complete sterilising immunity to HIV. However, there exists a small group of individuals that do not progress in the absence of antiviral therapy, these individuals are referred to as HIV controllers. They are divided into groups of individuals that maintain healthy CD4 T cell counts (>500 cells/μL) for over 10 years without therapy and remain asymptomatic and are termed long-term

Conclusions

HIV-1 presents a formidable and unprecedented challenge to the immune system. There is no natural immunity to HIV, but there are consistent themes of the types and functions of HIV-specific CD4 and CD8 T cells that partially control HIV infection and delay disease progression. Quality rather than quantity is an important factor of these HIV-specific cells, with polyfunctionality, increased expression of cytotoxic molecules and regulation of key transcriptional factors a key to their success. In

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This work was supported by the Australian National Health and Medical Research Council (NHMRC) Program Grant 510488 (CMLM, ADK, SJK and RDR), practitioner fellowship 10220536 (ADK), research fellowship 455350 (SJK) and career development fellowship APP1011578 (RDR). The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales.

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