Abstracts of Current Research
The role of mucosal and non-mucosal dendritic cells (DCs) in the elicitation of pathogen-specific T cell response
Protective immunity against viral and intracellular bacterial pathogens depends on the generation and maintenance of pathogen-specific CD4+ and CD8+ T cells. Dendritic cells (DC), which are the most efficient antigen-presenting cells, must be able to sample the peripheral microenvironment and migrate towards the draining lymph node where they activate naïve lymphocytes. Upon activation, pathogen-specific T cells undergo clonal expansion, generating effector cells that, through cell-mediated cytolysis and cytokine production, defend the host against the immunological insult. DCs are a complex cell population in mucosl and non-mucosal tissues that differ in their anatomic location, antigen recognition, processing machinery, and migratory capacity. This suggest that each DC subset may have a unique function in immune induction and regulation In additon, i t has became evident that the role of tissue-derived DCs in immune induction depends, in part, on the nature of the immunological insult . Our laboratory invasigates the contribution of the variuos DC subsets in the skin, oral mucosa and lung mucosa to T-cell priming following viral and bacterial infection.
- Furmanov, K., Elnekave, M., Lehmann, D., Clausen, BE. Kotton, DN and Hovav, A.H. The role of skin-derived dendritic cells in CD8+ T-cell priming following immunization with lentivectors. J Immuonl, (Submitted) .
- Wilson, A. A., G. J. Murphy, H. Hamakawa, L. W. Kwok, S. Srinivasan, A. H. Hovav, R. C. Mulligan, S. Amar, B. Suki, and D. N. Kotton. 2009. Amelioration of emphysema in mice via lentiviral transduction of long-lived pulmonary alveolar macrophages. J Clin Invest, (In press) .
- Hovav, A. H., M. Santosuosso, M. Bivas-Benita, A. Plair, A. Cheng, M. Elnekave, E. Righi, T. Chen, S. Kashiwagi, M. W. Panas, S. H. Xiang, K. Furmanov, N. L. Letvin, and M. C. Poznansky. 2009. X4 human immunodeficiency virus type 1 gp120 down-modulates expression and immunogenicity of codelivered antigens. J Virol 83:10941 .
- Elnekave, M., M. Bivas-Benita, G. O. Gillard, P. Sircar, and A. H. Hovav. 2009. A matter of timing: unsynchronized antigen expression and antigen presentation diminish secondary T cell responses. J Immunol 183:1013 .
- Wilson, A. A., L. W. Kwok, A. H. Hovav, S. J. Ohle, F. F. Little, A. Fine, and D. N. Kotton. 2008. Sustained expression of alpha1-antitrypsin after transplantation of manipulated hematopoietic stem cells. Am J Respir Cell Mol Biol 39:133 .
- Geiben-Lynn, R., J. R. Greenland, K. Frimpong-Boateng, N. van Rooijen, A. H. Hovav, and N. L. Letvin. 2008. CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T-cell immune responses. Blood 112:4585 .
- Hovav, A. H., M. W. Panas, S. Rahman, P. Sircar, G. Gillard, M. J. Cayabyab, and N. L. Letvin. 2007. Duration of antigen expression in vivo following DNA immunization modifies the magnitude, contraction, and secondary responses of CD8+ T lymphocytes. J Immunol 179:6725 .
- Hovav, A. H., M. W. Panas, C. E. Osuna, M. J. Cayabyab, P. Autissier, and N. L. Letvin. 2007. The impact of a boosting immunogen on the differentiation of secondary memory CD8+ T cells. J Virol 81:12793 .
- Hovav, A. H., M. J. Cayabyab, M. W. Panas, S. Santra, J. Greenland, R. Geiben, B. F. Haynes, W. R. Jacobs, Jr., and N. L. Letvin. 2007. Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis. J Virol 81:74 .
- Barenholz, A., A. H. Hovav, Y. Fishman, G. Rahav, J. M. Gershoni, and H. Bercovier. 2007. A peptide mimetic of the mycobacterial mannosylated lipoarabinomannan: characterization and potential applications. J Med Microbiol 56:579 .
- Hovav, A. H., J. Mullerad, A. Maly, L. Davidovitch, Y. Fishman, and H. Bercovier. 2006. Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein. Microbes Infect 8:1750 .
- Hovav, A. H., and H. Bercovier. 2006. Pseudo-rationale design of efficient TB vaccines: lesson from the mycobacterial 27-kDa lipoprotein. Tuberculosis (Edinb) 86:225 .
- Cayabyab, M. J., A. H. Hovav, T. Hsu, G. R. Krivulka, M. A. Lifton, D. A. Gorgone, G. J. Fennelly, B. F. Haynes, W. R. Jacobs, Jr., and N. L. Letvin. 2006. Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env. J Virol 80:1645 .
- Hovav, A. H., Y. Fishman, and H. Bercovier. 2005. Gamma interferon and monophosphoryl lipid A-trehalose dicorynomycolate are efficient adjuvants for Mycobacterium tuberculosis multivalent acellular vaccine. Infect Immun 73:250 .
- Hovav, A. H., L. Davidovitch, G. Nussbaum, J. Mullerad, Y. Fishman, and H. Bercovier. 2004. Mitogenicity of the recombinant mycobacterial 27-kilodalton lipoprotein is not connected to its antiprotective effect. Infect Immun 72:3383 .
- Hovav, A. H., J. Mullerad, L. Davidovitch, Y. Fishman, F. Bigi, A. Cataldi, and H. Bercovier. 2003. The Mycobacterium tuberculosis recombinant 27-kilodalton lipoprotein induces a strong Th1-type immune response deleterious to protection. Infect Immun 71:3146 .