CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes.
We studied whether signaling through CD30, a member of the TNF receptor family, affected acute infection with HIV-1, encompassing its entire replicative cycle. Several non-Hodgkin cell lines, targets of CXCR4-dependent (X4) HIV-1 infection, were positive for CD30 expression. CD30 ligation induced up-regulation of viral replication only in certain CD30+ cell lines. Enhancement of X4 virus replication by CD30 engagement inversely correlated with both CD30 surface density and constitutive NF-kappaB activation. Conversely, expression of CD30, but not of other members of the TNF receptor family, was proportional to constitutive NF-kappaB binding. Concomitantly, secretion of soluble (s) CD30 increased in all cell lines by CD30 ligation. sCD30 release was enhanced by engagement of CD30 alone and, to a greater extent, by co-engagement of CD3 also in primary gamma delta T lymphocytes, along with complementary modulations of their surface CD30 expression. sCD30-containing supernatant specifically inhibited HIV-1 expression induced by CD30 engagement in chronically infected ACH-2 T cells; thus sCD30 may act as a negative feed-back molecule. In conclusion, we have delineated novel features of CD30 biology and underline the peculiar link of CD30 expression to constitutive NF-kappaB activation which is pivotal to both HIV replication and cell survival.
Laboratory of Clinical Immunology, Scientific Institute H San Raffaele, Milan, Italy. biswas.priscilla@hsr.it
Priscilla
P
Biswas
Barbara
B
Mantelli
Fanny
F
Delfanti
Marina
M
Ferrarini
Guido
G
Poli
Adriano
A
Lazzarin
D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
D017730:Ki-1 Antigen; D016328:NF-kappa B; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019718:Receptors, CXCR4