Allogeneic cell stimulation enhances cytomegalovirus replication in the early period of primary infection in an experimental rat model.
BACKGROUND
Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined.


METHODS
Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues.


RESULTS
The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland.


CONCLUSIONS
Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.
Tamura
Kazuki
K
First Department of Surgery, Nagasaki University School of Medicine, Nagasaki, Japan.
Oka
Tadayuki
T
Ohsawa
Kazutaka
K
Koji
Takehiko
T
Watanabe
Yoji
Y
Katamine
Shigeru
S
Sato
Hiroshi
H
Ayabe
Hiroyoshi
H
D000477:Alkylating Agents / Q000009:adverse effects; D000818:Animals; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000150:complications* / Q000503:physiopathology*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D016685:Mitomycin / Q000009:adverse effects; D051381:Rats; D011920:Rats, Inbred WF; D013154:Spleen / Q000187:drug effects / Q000503:physiopathology*; D013268:Stimulation, Chemical; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D000477:Alkylating Agents; D016685:Mitomycin