1. Chimpanzee CD4+ T cells are relatively insensitive to HIV-1 envelope-mediated inhibition of CD154 up-regulation
- Author
-
Babs E. Verstrepen, Sam O. Hofman, Erik Rutjens, Jonathan L. Heeney, Gerrit Koopman, Joost N. Vermeulen, Indresh K. Srivastava, Jan M. Prins, Graduate School, Amsterdam institute for Infection and Immunity, and Infectious diseases
- Subjects
CD4-Positive T-Lymphocytes ,Pan troglodytes ,medicine.medical_treatment ,T cell ,CD40 Ligand ,Immunology ,HIV Infections ,chemical and pharmacologic phenomena ,Biology ,Sensitivity and Specificity ,Interleukin 21 ,Immune system ,Species Specificity ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,CD154 ,Immunodeficiency ,env Gene Products, Human Immunodeficiency Virus ,CD28 ,medicine.disease ,Virology ,Up-Regulation ,Cytokine ,medicine.anatomical_structure ,CD4 Antigens ,Chronic Disease ,HIV-1 ,Interleukin-2 ,Protein Binding - 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.
- Published
- 2008