RESULTS: Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge.
CONCLUSIONS: In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.
METHODS: The pathogenic potential of HeV and both strains of NiV (Malaysia, Bangladesh) was assessed in cynomolgus monkeys and compared with henipavirus-infected historical control AGMs. Multiplex gene and protein expression assays were used to compare host responses.
RESULTS: In contrast to AGMs, in which henipaviruses cause severe and usually lethal disease, HeV and NiVs caused only mild or asymptomatic infections in macaques. All henipaviruses replicated in macaques with similar kinetics as in AGMs. Infection in macaques was associated with activation and predicted recruitment of cytotoxic CD8+ T cells, Th1 cells, IgM+ B cells, and plasma cells. Conversely, fatal outcome in AGMs was associated with aberrant innate immune signaling, complement dysregulation, Th2 skewing, and increased secretion of MCP-1.
CONCLUSION: The restriction factors identified in macaques can be harnessed for development of effective countermeasures against henipavirus disease.
METHODS: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord-derived MSCs (UC-MSCs) on activated T cells.
RESULTS: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed.
CONCLUSIONS: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells.
OBJECTIVE: In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors.
METHODS: Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction.
RESULTS: BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH.
CONCLUSION: These findings suggest the potential of BBP as a potent immunosuppressive agent.