Abstract:
BACKGROUND:Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined. METHODS:To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murine donor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining. RESULTS:By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells. CONCLUSIONS:In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.
journal_name
Transplantationjournal_title
Transplantationauthors
Shimamura M,Saunders U,Rha B,Guo L,Cassady KA,George JF,Britt WJdoi
10.1097/TP.0b013e31822c6e89subject
Has Abstractpub_date
2011-10-15 00:00:00pages
759-66issue
7eissn
0041-1337issn
1534-6080journal_volume
92pub_type
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