Mechanisms of immunopathology mediated by RSV-specific CD4 T cells

My research focuses on the CD4 T cell response to respiratory syncytial virus (RSV). A vaccine for RSV was tested in children in the 1960’s and was found to result in increased morbidity and mortality upon subsequent natural infection with RSV. Using a BALB/c mouse model of vaccination with a recombinant vaccinia virus expressing a single RSV protein, we can re-create the vaccine-enhanced disease seen in humans. My projects investigate the mechanisms that cause enhanced disease and pulmonary eosinophilia upon RSV infection of vaccinated hosts. We have shown that IL-13 recruits eosinophils into the lungs of BALB/c mice vaccinated with the attachment (G) protein of RSV through CCL11 and CCL22. We have identified a CD4 T cell epitope in the fusion (F) protein of RSV, which does not induce pulmonary eosinophilia, and demonstrate that F-specific CD4 T cells are funtionally different from G-specific CD4 T cells.

Monick MM, Powers LS, Hassan I, Groskreutz D, Yarovinsky TO, Barrett CW, Castilow EM, Tifrea D, Varga SM, Hunninghake GW. Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17. J Immunol. 2007 Aug 1;179(3):1648-58. PubMed PMID: 17641031.

Meyerholz DK, Rodgers J, Castilow EM, Varga SM. Alcian Blue and Pyronine Y histochemical stains permit assessment of multiple parameters in pulmonary disease models. Vet Pathol. 2009 Mar;46(2):325-8. doi: 10.1354/vp.46-2-325. PubMed PMID: 19261646; PubMed Central PMCID: PMC2802330.

Meyerholz DK, Griffin MA, Castilow EM, Varga SM. Comparison of histochemical methods for murine eosinophil detection in an RSV vaccine-enhanced inflammation model. Toxicol Pathol. 2009 Feb;37(2):249-55. doi: 10.1177/0192623308329342. Epub 2009 Jan 29. PubMed PMID: 19181630; PubMed Central PMCID: PMC2664312.

Castilow EM, Varga SM. Overcoming T cell-mediated immunopathology to achieve safe RSV vaccination. Future Virol. 2008;3(5):445-454. PubMed PMID: 19057653;PubMed Central PMCID: PMC2593094.

Castilow EM, Legge KL, Varga SM. Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease. J Immunol. 2008 Nov 15;181(10):6692-6. PubMed PMID: 18981084; PubMed Central PMCID: PMC2596668.

Castilow EM, Meyerholz DK, Varga SM. IL-13 is required for eosinophil entry into the lung during respiratory syncytial virus vaccine-enhanced disease. J Immunol. 2008 Feb 15;180(4):2376-84. PubMed PMID: 18250447.

Castilow EM, Olson MR, Varga SM. Understanding respiratory syncytial virus (RSV) vaccine-enhanced disease. Immunol Res. 2007;39(1-3):225-39. Review. PubMed PMID: 17917067.

Castilow EM, Olson MR, Meyerholz DK, Varga SM. Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus. J Virol. 2008 Mar;82(5):2196-207. Epub 2007 Dec 19. PubMed PMID:18094193; PubMed Central PMCID: PMC2258940.