Protective versus pathogenic anti-CD4 immunity: insights from the study of exposed seronegative individuals with natural resistance to HIV infection
HIV-1 exposure determines several dramatic unbalances in the immune system homeostasis. Here, we will focus on the paradox whereby CD4 specific autoimmune responses, which are expected to contribute to the catastrophic loss of most part of the T helper lymphocyte subset in infected patients, may display the characteristics of an unconventional protective immunity in individuals naturally resistant to HIV-1 infection.
Reference to differences in fine epitope mapping of these two oppositely polarized outcomes will be presented, with particular reference to partially or totally CD4-gp120 complex-specific antibodies. The fine tuning of the anti-self immune response to the HIV-1 receptor may contribute to determine whether viral exposure will bring to infection or, alternatively, to a protective immunity.Along this line, an efficacious anti-HIV strategy can rely on the active (i.e ., through immunization) or passive targeting of cryptic epitopes of the CD4-gp120 complex, including those harboured within the CD4 molecule.
Such epitopes are expected to be safe from genetic drift and thus allow for broad spectrum of efficacy. Moreover, since these epitopes are not routinely exposed in uninfected individuals, they are expected to become targets of neutralizing antibodies or other specifically designed molecules only after viral exposure, with a predictable low impact in terms of potentially harmful anti-CD4 self-reactivity.The experimentum naturae of naturally resistant individuals indicates a strategy to design innovative strategies to neutralize HIV-1 by acting on the sharpen edge between harmful and protective self-reactivity.
Author: Samuele BurasteroMariangela FiginiBarbara FrigerioPaolo LussoLuca MollicaLucia Lopalco
Credits/Source: Journal of Translational Medicine 2009, 7:101
Published on: 2009-11-28
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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