Chronic HIV infection in patients receiving antiretroviral therapy is associated with elevated plasma markers of inflammation and activation of NK cells1 and monocytes2. This may increase risk of non-AIDS co-morbidities such as cardiovascular disease and non-AIDS cancers, known to be elevated in these individuals. The causes of innate immune activation in the setting of virological suppression are unclear.
We have shown that NK cells are activated both phenotypically (elevated expression of HLA-DR) and functionally (increased spontaneous degranulation measured by CD107a surface expression) in virologically suppressed HIV+ individuals. NK cells also lose expression of CD16 which mediates antibody-dependent cellular cytotoxicity. The cause of NK activation in these patients is unknown but is not associated with HIV viremia or with CD4 counts. It is however associated with markers of inflammation (soluble CD14, neopterin and plasma LPS)1.
We have identified a novel NK cell population (γ- NK) in HIV+ patients which can account for up to 90% of total NK cells. γ- NKs lose expression of the ITAM-containing signaling adaptor molecule FcRγ, but have normal expression of the homologous signaling adapter TCRζ. γ- NKs have recently been described as being generated specifically in response to CMV infection or reactivation3 but their prevalence is increased dramatically by HIV co-infection and not decreased following suppression of HIV viremia with antiretroviral therapy. We have shown that γ- NKs in HIV+ individuals have an altered and highly skewed repertoire of activating receptors and altered senescence and maturation markers.
CMV reactivation is associated with immune activation and changes to NK cell populations in virologically suppressed HIV infected individuals. We are currently studying the properties of γ- NKs to understand the significance of such a dramatic skewing of the NK population to NK cell mediated killing and anti-tumour responses.
1. Lichtfuss et al (2012) The J Immunol 189 ,1491
2. Hearps et al (2012) AIDS 26, 843
3. Zhang et al (2013)J. Immunol 190, 1402