The role of co-stimulation in regulation of chemokine receptor expression and HIV-1 infection in primary T lymphocytes.
Fusion and entry of the human immunodeficiency virus (HIV) into CD4(+) T lymphocytes requires expression of CD4 and a coreceptor. At least eight chemokine receptors can serve as coreceptors for HIV. Accumulating evidence indicates that multiple factors, including the state of cellular differentia- tion and activation, regulate the expression of alpha- and beta-chemokine receptors on lymphocytes. For example, binding of antibodies to the CD28 coreceptor can downregulate expression of beta-chemokine receptors, and this appears to have important consequences on the susceptibility of CD4(+) T lymphocytes to infection by HIV-1. In contrast, binding of the natural CD28 ligand B7 or antibodies to the CD28 homologue CTLA-4 can upregulate CCR5 expression, sug- gesting a reciprocal interaction between CD28 and CTLA-4 and the regulation of beta-chemokine receptor expression. Thus, the CD28/CTLA-4/B7 co-stimulation pathway is identi- fied as a potential novel target for the control of susceptibility to some strains of HIV-1 infection.
Carroll
R G
RG
Henry M. Jackson Foundation, Military HIV Research Program, Bethesda, MD, 20889, USA.
Riley
J L
JL
Levine
B L
BL
Blair
P J
PJ
St Louis
D C
DC
June
C H
CH
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D018925:Chemokines / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D019713:Receptors, CCR5 / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology*; D011991:Receptors, Virus / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018925:Chemokines; D018796:Immunoconjugates; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D000069594:Abatacept