Cynomolgus macaques (Macaca fascicularis) infected with a human HPAI H5N1 virus isolate (A/Vietnam/1203/2004), or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection, with inflammation peaking on days 2-4 pi in the 1918 reassortant groups, followed by resolution. In contrast, no cessation of inflammation was apparent in the H5N1 group [23] . Grossly, the most notable extrapulmonary changes occurred in the lymph nodes. The retropharyngeal and tracheobronchial lymph nodes appeared mildly to moderately enlarged after all of the influenza virus infections, most notably on days 4 and 7 pi. Early in the infections, there was variable edema of the lymph nodes, and by day 4 and 7 pi, the nodes in the HANA, HANANS and A/Texas groups were characterized microscopically by marked follicular and paracortical hypertrophy. In contrast, the follicles in the lymph nodes of H5N1-infected animals were involuting and appeared with variable degrees of hyalinization of the germinal centers, except at 7 days pi, where there were signs of follicular hypertrophy in the one surviving animal. Only in the H5N1-infected animals was there histological evidence of tonsil involvement, with frank neutrophilic and necrotizing tonsillitis on days 1 and 2 pi (Fig. 1a) . By day 7, the inflammation was resolving. Notably, the histopathological changes in the lymph nodes and tonsils of the H5N1-infected animals correlated with the extent of virus infection as detected by IHC (exemplified by the tonsil in Fig. 1b) . A few virus-infected cells were found in the tonsil and retropharyngeal lymph nodes of HANA-infected animals on day 1 pi (not shown). No virus-infected cells were detected in these tissues in any animal of the other groups. The number of CD83-positive cells in lymph nodes and tonsil either remained within normal levels or increased over time in the HANA, HANANS and A/Texas groups, while these cells decreased in frequency and intensity of labeling in the tissues of the H5N1 animals (Fig. 1d) . The disappearance of CD83-positive cells from the lymphoid tissues of the H5N1-infected animals over time correlated temporally with a pronounced occurrence of apoptotic cells, as reflected by expression of activated caspase 3 (Fig. 1f) .