Current HIV/AIDS Reports

, Volume 8, Issue 1, pp 4–11 | Cite as

Revisiting Immune Exhaustion During HIV Infection

  • Alka Khaitan
  • Derya Unutmaz


Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of immune activation remain unclear. Persistent antigenic stimulation during HIV infection may also lead to immune exhaustion, a phenomenon in which effector T cells become dysfunctional and lose effector functions and proliferative capacity. Several markers of immune exhaustion, such as PD-1, LAG-3, Tim-3, and CTLA-4, which are also negative regulators of immune activation, are preferentially upregulated on T cells during HIV infection. It is not yet clear whether accumulation of T cells expressing activation inhibitory molecules is a consequence of general immune or chronic HIV-specific immune activation. Importantly, however, in vitro blockade of PD-1 and Tim-3 restores HIV-specific T-cell responses, indicating potential for immunotherapies. In this review we discuss the evolution of our understanding of immune exhaustion during HIV infection, highlighting novel markers and potential therapeutic targets.


T-cell exhaustion Immune activation PD-1 Tim-3 HIV LAG-3 SIV 



This work was supported by NIH grant R21AI087973-01 to DU and the NYU Physician Scientist Training Program award to AK, supported in part by grant 1 UL1 RR029893 from the National Center for Research Resources, National Institutes of Health.


No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PediatricsNew York University School of MedicineNew YorkUSA
  2. 2.Department of MicrobiologyNew York University School of MedicineNew YorkUSA
  3. 3.Department of PathologyNew York University School of MedicineNew YorkUSA
  4. 4.Department of MedicineNew York University School of MedicineNew YorkUSA
  5. 5.New York University Langone Medical CenterNew YorkUSA

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