Evolution of Innate and Adaptive Effector Cell Functions during Acute HIV‐1 Infection

Abstract

Early events during acute human immunodeficiency virus type 1 (HIV-1) infection are critical in determining the course of disease progression. Cells of the innate and adaptive immune responses are involved in this acute response to infection; however, little is known about the coevolution of innate and adaptive effector cell populations during the initial phase of HIV-1 infection. Here, we have characterized the development of innate natural killer (NK) cell and adaptive HIV-1-specific CD8(+) T cell function during acute HIV-1 infection. Although NK cell populations were significantly expanded during acute infection before HIV-1 seroconversion, HIV-1-specific CD8(+) T cell responses were absent or weak and were inversely correlated with the level of NK cell activity. NK cell activity was directly correlated with the level of viral replication during acute HIV-1 infection and declined rapidly in subjects who initiated highly active antiretroviral therapy, whereas NK cell activity remained elevated in subjects who did not initiate therapy. Yet, reexposure to HIV-1 antigen during treatment discontinuation in chronic infection resulted in a synchronous increase in NK and CD8(+) T cell activity. Overall, these data demonstrate that expansion of the NK cell population precedes the development of adaptive HIV-1-specific CD8(+) T cells during acute infection but that both effector cell subsets respond with similar kinetics during chronic HIV-1 infection.

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

“…A systematic review of these studies suggests that natural resistance to HIV infection in highly exposed individuals is mediated by multiple mechanisms, conferring on them an ''immunologic advantage'' that may be related to innate and/or adaptive immune systems. 66,67 Although offering only a partial explanation to the natural resistance to HIV infection, 68 observations in female sex workers in Nairobi with frequent HIV exposure, [69][70][71] in exposed uninfected infants with strong HIV-1-specific T cell responses, 72 and more recently in discordant couples 73 suggest that recurrent viral exposure may lead to priming of HIV-specific systemic and mucosal immune responses. These findings suggest that persons receiving PrEP who are exposed to HIV may generate HIV-specific T cell responses, potentially contributing to protection against the establishment of HIV infection.…”

Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

“…Accumulating evidence suggests that earliest immunological responses that result in early containment of viral replication determine the rate of disease progression [6]. Thus, the data presented here imply that NK cells may mediate the bulk of their antiviral activity in the peripheral circulation, rather than in LNs, where robust early viral control may help prevent dissemination of the virus.…”

“…Following acute infection, viral replication in the peripheral circulation is brought down within the first few weeks of infection to a viral setpoint [4], at a time when adaptive immune responses are just being induced [5,6]. Thus, it is likely that innate immune mechanisms, including natural killer (NK) cells, may play a critical role in the early control of viral replication.…”

“…NK cells expand rapidly following acute HIV-1 infection [6], and KIR-expressing NK cells have been implicated in both direct and indirect control of HIV-1 replication in vitro [10]. Given that HIV replicates profusely within LNs during early infection, early antiviral effector cells such as NK cells might play a critical role in the early control of HIV viral replication.…”

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…(table 1). Once established, HIV-1 infection is accompanied by an expansion of NK cells [54]. However, a skewed distribution of NK cell subpopulations and loss of cell functions occur as a consequence of exposure to HIV-1 [55].…”