The human uniqueness of HIV: Innate immunity and the viral Tat protein

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period o f post-infection latency, the titers of those natural antibodies decline an d other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with H IV Tar protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparen t:ly induced Tar-reactive antibodies do arise. Evidence of a temporal relat ionship between the decline of the Tat reactive natural antibodies and prog ression of HIV pathogenesis, including demise of CD4(+)T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tar-related pathogenicity may be limited by th e immune system recognition of the natural antibody-reactive sequences of T at as "self" with consequent induction of tolerance and restrict ion of pro duction of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resi stance to tolerance-based diminishment of the protective natural antibodies . Although not yet defined, that characteristic may be shared by the occasi onally observed HIV+ humans known as LTNP (longterm-nonprogressors). (C) Am erican Society for Histocompatibility and Immunogenetics, 1999 Published by Elsevier Science Inc.