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Chimpanzee CD4+ T cells are relatively insensitive to HIV-1 envelope-mediated inhibition of CD154 up-regulation.

Rutjens, Erik and Vermeulen, Joost and Verstrepen, Babs and Hofman, Sam and Prins, Jan M and Srivastava, Indresh and Heeney, Jonathan L and Koopman, Gerrit (2008) Chimpanzee CD4+ T cells are relatively insensitive to HIV-1 envelope-mediated inhibition of CD154 up-regulation. European Journal of Immunology, 38 (4). pp. 1164-1172. ISSN 0014-2980

Abstract

CD40-CD154 interaction forms a key event in regulation of crosstalk between dendritic cells and CD4 T cells. In human immunodeficiency virus (HIV)-1 infected patients CD154 expression is impaired, and the resulting loss of immune responsiveness by CD4+ T cells contributes to a progressive state of immunodeficiency in humans. Although chimpanzees are susceptible to chronic HIV-1/SIVcpz infection, they are relatively resistant to the onset of AIDS. This relative resistance is characterized by maintenance of CD4+ T cell populations and function, which is highly compromised in human patients. In our cohort of chronically HIV-1- and SIVcpz-infected chimpanzees, we demonstrated the capacity to produce IL-2, following CD3/CD28 stimulation, as well as preserved CD154 up-regulation. Cross-linking of CD4 with mAb was found to inhibit CD3/CD28-induced up-regulation of CD154 equally in chimpanzees and humans. However, specific cross-linking with trimeric recombinant HIV-1 gp140 revealed reduced sensitivity for inhibition of CD154 up-regulation in chimpanzees, requiring fourfold higher concentrations of viral protein. Chimpanzee CD4+ T cells are thus less sensitive to the immune-suppressive effect of low-dose HIV-1 envelope protein than human CD4+ T cells.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); On personal web site or secure external website at authors institution; Publisher's version/PDF cannot be used
Keywords: Chimpanzee; CD154; Cytokine; HIV-1; Pathogenesis
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Date Deposited: 14 Dec 2009 13:52
Last Modified: 14 Dec 2009 13:52
URI: https://oak.novartis.com/id/eprint/875

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