Ryan Ahern

Publications (2)32.42 Total impact

• Article: Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction.

  Daniel E Kaufmann, Daniel G Kavanagh, Florencia Pereyra, John J Zaunders, Elizabeth W Mackey, Toshiyuki Miura, Sarah Palmer, Mark Brockman, Almas Rathod, Alicja Piechocka-Trocha, [......], Baogong Zhu, Sylvie Le Gall, Michael T Waring, Ryan Ahern, Kristin Moss, Anthony D Kelleher, John M Coffin, Gordon J Freeman, Eric S Rosenberg, Bruce D Walker
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  ABSTRACT: In progressive viral infection, antiviral T cell function is impaired by poorly understood mechanisms. Here we report that the inhibitory immunoregulatory receptor CTLA-4 was selectively upregulated in human immunodeficiency virus (HIV)-specific CD4(+) T cells but not CD8(+) T cells in all categories of HIV-infected subjects evaluated, with the exception of rare people able to control viremia in the absence of antiretroviral therapy. CTLA-4 expression correlated positively with disease progression and negatively with the capacity of CD4(+) T cells to produce interleukin 2 in response to viral antigen. Most HIV-specific CD4(+) T cells coexpressed CTLA-4 and another inhibitory immunoregulatory receptor, PD-1. In vitro blockade of CTLA-4 augmented HIV-specific CD4(+) T cell function. These data, indicating a reversible immunoregulatory pathway selectively associated with CD4(+) T cell dysfunction, provide a potential target for immunotherapy in HIV-infected patients.
  Nature Immunology 12/2007; 8(11):1246-54. · 26.01 Impact Factor
• Article: Evolution of innate and adaptive effector cell functions during acute HIV-1 infection.

  Galit Alter, Nickolas Teigen, Ryan Ahern, Hendrik Streeck, Angela Meier, Eric S Rosenberg, Marcus Altfeld
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  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.
  The Journal of Infectious Diseases 06/2007; 195(10):1452-60. · 6.41 Impact Factor