Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells
Jinjong Myoung, Don Ganem
Jinjong Myoung, Don Ganem
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Research Article

Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells

Abstract

Kaposi sarcoma–associated herpesvirus (KSHV) is a B-lymphotropic virus whose primary site of replication is the oropharynx. KSHV can infect both T and B cells from primary tonsillar explant cultures. However, T cells do not support lytic replication, while B cells spontaneously produce substantial amounts of infectious virus. Here, we provide evidence for a mechanism by which activated T cells may promote or stabilize latency of KSHV infection in B cells. When mixed cultures of B cells and activated T cells were exposed to KSHV, little spontaneous virus production was observed. Removing T cells from the mix or treating the mixed culture with immune suppressants enhanced virus production. Adding back activated T cells to purified infected B cells efficiently suppressed KSHV production, primarily due to CD4+ T cells. This suppressive activity required T cell activation and direct cell-cell contact, but not prior exposure to KSHV antigen. Suppression was not MHC restricted and did not result in killing of the target cell. We therefore propose that oropharyngeal T cells activated by a variety of stimuli can recognize ligands on infected target B cells, leading to signaling events that prevent spontaneous lytic activation and promote latent infection in this compartment.

Authors

Jinjong Myoung, Don Ganem

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Figure 7

TCR stimulation confers inhibitory activity on T cells.

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TCR stimulation confers inhibitory activity on T cells. (A) Unfractionat...
(A) Unfractionated tonsillar cells were prestimulated (left panel) or left untreated (right panel) by PHA (10 μg/ml) for 6 hours and infected with rKSHV.219 at MOI 3 for 6 or 12 hours. After extensive wash, infected cultures were treated with stimulatory antibodies (10 μg/ml) to different cell surface molecules for 3 successive days as indicated. Different isotype antibody controls and medium alone resulted in similar results, and medium alone is shown. IUs in the culture supernatants, with background subtracted, were determined as before. The mean of data from 5 different tonsils is indicated by the horizontal bar. (B) MLR was induced by mixing tonsillar cells from 2 different individuals (see Methods) for the indicated days. T cells were purified from the mixed cultures and added into infected B cells. Relevant control cells from the same donor were included (left panel) for comparison. IUs were determined as before and normalized to those of the medium alone control and plotted as percentage of control (y axis). Dots represent data from individual tonsils. The mean of data from 7 different tonsils is indicated by the horizontal bar. *P < 0.05; ***P < 0.001 by Student’s t test.