Chimpanzee CD4+ T cells are relatively insensitive to HIV-1 envelope-mediated inhibition of CD154 up-regulation.
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.
Rutjens
Erik
E
Biomedical Primate Research Centre, Department of Virology, Rijswijk, The Netherlands.
Vermeulen
Joost
J
Verstrepen
Babs
B
Hofman
Sam
S
Prins
Jan M
JM
Srivastava
Indresh
I
Heeney
Jonathan L
JL
Koopman
Gerrit
G
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D023201:CD40 Ligand / Q000378:metabolism*; D002908:Chronic Disease; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D002679:Pan troglodytes / Q000276:immunology* / Q000821:virology; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013045:Species Specificity; D015854:Up-Regulation / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism*
D015704:CD4 Antigens; D007376:Interleukin-2; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D023201:CD40 Ligand