TY - JOUR
T1 - Early increase of CD4+ CD45RA+ and CD4+ CD95- cells with conserved repertoire induced by anti-retroviral therapy in HIV-infected patients
AU - Silvestri, G.
AU - Munoz-Calleja, C.
AU - Bagnarelli, P.
AU - Piedimonte, G.
AU - Clementi, M.
AU - Montroni, M.
PY - 1998
Y1 - 1998
N2 - Administration of anti-retroviral drugs induces a decrease of vital load associated with increase of CD4+ cell count in most HIV-infected patients. To investigate the early changes in CD4+ cell phenotype induced by anti- retroviral therapy, six patients with CD4+ cell count > 100/mm3 and never treated with anti-HIV therapy were enrolled and blood samples collected several times within 14 days from the initiation of therapy with Zidovudine plus Didanosine. CD4+ cell count and HIV viraemia were investigated at each time point, as well as the expression of CD45RA, CD45RO and CD95/Fas molecules on CD4+ cells, and the T cell receptor (TCR) Vβ repertoire of CD4+ cells. All patients showed a rapid and dramatic decrease in vital load with a corresponding increase of CD4+ cell count. The main remodelling of CD4+ cell subpopulations took place in the first 14 days of therapy, and consisted of: (i) increased CD4+ CD45RA+/CD4+ CD45RO+ ratio; (ii) decrease of CD95/Fas expression. The rise in absolute number of CD4+CD45RA+ cells was paralleled by an increase of CD4+ CD95/Fas- cells and accounted for most of the early increment of CD4+ cell count. The TCR Vβ repertoire of CD4+ cells was conserved after anti-HIV therapy, with the exception of two patients with expanded CD4+ Vβ12+ cells, which also tested CD45RA+ and CD95/Fas-. These experiments show that newcomer CD4+ lymphocytes are CD45RA+ CD95/Fas- cells, suggesting that blocking HIV replication causes an early and antigen-independent proliferation of possibly 'naive' cells unprimed for CD95/Fas-mediated apoptosis. These cells expressed a conserved and widespread TCR repertoire, suggesting that their capability for antigenic recognition is intact.
AB - Administration of anti-retroviral drugs induces a decrease of vital load associated with increase of CD4+ cell count in most HIV-infected patients. To investigate the early changes in CD4+ cell phenotype induced by anti- retroviral therapy, six patients with CD4+ cell count > 100/mm3 and never treated with anti-HIV therapy were enrolled and blood samples collected several times within 14 days from the initiation of therapy with Zidovudine plus Didanosine. CD4+ cell count and HIV viraemia were investigated at each time point, as well as the expression of CD45RA, CD45RO and CD95/Fas molecules on CD4+ cells, and the T cell receptor (TCR) Vβ repertoire of CD4+ cells. All patients showed a rapid and dramatic decrease in vital load with a corresponding increase of CD4+ cell count. The main remodelling of CD4+ cell subpopulations took place in the first 14 days of therapy, and consisted of: (i) increased CD4+ CD45RA+/CD4+ CD45RO+ ratio; (ii) decrease of CD95/Fas expression. The rise in absolute number of CD4+CD45RA+ cells was paralleled by an increase of CD4+ CD95/Fas- cells and accounted for most of the early increment of CD4+ cell count. The TCR Vβ repertoire of CD4+ cells was conserved after anti-HIV therapy, with the exception of two patients with expanded CD4+ Vβ12+ cells, which also tested CD45RA+ and CD95/Fas-. These experiments show that newcomer CD4+ lymphocytes are CD45RA+ CD95/Fas- cells, suggesting that blocking HIV replication causes an early and antigen-independent proliferation of possibly 'naive' cells unprimed for CD95/Fas-mediated apoptosis. These cells expressed a conserved and widespread TCR repertoire, suggesting that their capability for antigenic recognition is intact.
KW - CD4+
KW - CD45RA/RO
KW - CD95/Fas
KW - HIV
KW - Lymphocytes
KW - TCR
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U2 - 10.1046/j.1365-2249.1998.00464.x
DO - 10.1046/j.1365-2249.1998.00464.x
M3 - Article
C2 - 9472655
AN - SCOPUS:0031951027
VL - 111
SP - 3
EP - 11
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 1
ER -