Lymphocytes delay kinetics of HSV-1 reactivation from in vitro explants oflatent infected trigeminal ganglia

A persistent immune response to herpes simplex virus type 1 (HSV-I) is evid enced by the expression of cytokine transcripts along with infiltrating mon onuclear cells in the ganglia of latently infected mice. in trigeminal gang lion (TG) explant co-cultures, the presence of nonirradiated or irradiated primed splenocytes significantly reduced HSV-I reactivation as defined by s ecreted infectious HSV-1 found in the supernatants of TG er;plant cultures. primed splenocytes depleted of CD4(+) or CD8(+) cells did not antagonize H SV-1 reactivation. Cytokines including interleukin (IL)-2, IL-6, lL-10, and IL-12 were all detected in the TG explant cultures containing splenocytes. To further study the role of cytokines in HSV-1 reactivation, dissociated TG cell cultures were treated with exogenous recombinant cytokines includin g IFN-alpha or -gamma, IL-4, 6, 10, 13, or tumor necrosis factor (TNF)-alph a at concentrations ranging from 2.0 pg to 2.0 ng/culture (or 0.3-300 units /culture for the IFNs). While no cytokines tested at any concentration sign ificantly modified HSV-1 reactivation, neutralizing antibody to IL-6, but n ot to IFN-alpha/beta, significantly antagonized HSV-I reactivation. Collect ively, the results suggest that IL-6 is directly or indirectly involved in HSV-1 reactivation in TG explant cultures. (C) 1999 Elsevier Science B.V. A ll rights reserved.