Protective immunity towards intracellular pathogens.
ABSTRACT Immunity towards intracellular pathogens is often dependent upon the generation of CD8(+) memory T cells, which provide long-lasting and effective protection. Over the past few years, we have gained novel insights into the heterogeneity of CD8(+) T cells, time points of lineage commitment, and lineage relationships between subpopulations. These studies suggest that memory CD8(+) T cells progressively develop from naïve cells early during the immune response and further differentiate unidirectionally into short-living effector cells. We have also learnt that different memory subsets play distinct roles in conferring protection: whereas effector memory T cells are able to provide immediate protection but are not necessarily maintained long-term, central memory T cells have the potential for constant self-renewal. Thus, neither subset really fulfills all criteria of memory. As protective effector memory cells can develop from central memory cells, vaccination strategies should focus on induction of a balanced ratio of the two memory T cell subsets.
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ABSTRACT: Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like Cytomegalovirus (CMV) reactivation. Since the success of todays' virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft versus host disease (GvHD), in particular in prophylactic settings after T cell-depleting allo-HSCT protocols. To establish a lower limit for successful adoptive T cell therapy, we conducted low dose CD8(+) T cell transfers in the well-established murine Listeria monocytogenes (L.m.) infection model. MHC-Streptamer-enriched antigen-specific CD62L(hi), but not CD62L(lo) CD8(+) memory T cells proliferated, differentiated and protected against L.m. infections after prophylactic application. Even progenies derived from one single CD62L(hi) L.m.-specific CD8(+) T cell could be protective against bacterial challenge. In analogy, low dose transfers of Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients led to strong pathogen-specific T cell expansion in a compassionate-use setting. In summary, low dose adoptive T cell transfer could be a promising strategy particularly for prophylactic treatment of infectious complications after allo-HSCT.Blood 05/2014; 124(4). DOI:10.1182/blood-2013-12-547349 · 9.78 Impact Factor
Article: Fiebelkorn, G.*, Polle, A.*, Ernst, D.: Untersuchungen von Genexpression und physiologischen Abwehrreaktionen an gesunden und geschädigten Buchen (Fagus sylvatica L.). Mitteilungen aus der Forschungsanstalt für Waldökologie und Forstwirtschaft Rheinland-Pfalz ; Nr. 59/06, Strategien zur Sicherung von Buchenwäldern, Petercord, R. ; Block, J. (Hrsg.), 111-118 (2006)
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ABSTRACT: A major goal for immunotherapy is to tolerize the immune cells that coordinate tissue damage in autoimmune and alloantigen responses. CD4 T cells play a central role in many of these conditions and improved antigen-specific regulation or removal of these cells could revolutionize current treatments. A confounding factor is that little is known about whether and how tolerance is induced in memory CD4 T cells. We used MHC class II tetramers to track and analyze a population of endogenous antigen-specific memory CD4 T cells exposed to soluble peptide in the absence of adjuvant. We found that such memory T cells proliferated and reentered the memory pool apparently unperturbed by the incomplete activation signals provided by the peptide. Upon further restimulation in vivo, CD4 memory T cells that had been previously exposed to peptide proliferated, provided help to primary responding B cells, and migrated to inflamed sites. However, these reactivated memory cells failed to survive. The reduction in T-cell number was marked by low expression of the antiapoptotic molecule B cell lymphoma 2 (Bcl2) and increased expression of activated caspase molecules. Consequently, these cells failed to sustain a delayed-type hypersensitivity response. Moreover, following two separate exposures to soluble antigen, no T-cell recall response and no helper activity for B cells could be detected. These results suggest that the induction of tolerance in memory CD4 T cells is possible but that deletion and permanent removal of the antigen-specific T cells requires reactivation following exposure to the tolerogenic antigen.Proceedings of the National Academy of Sciences 05/2014; 111(21). DOI:10.1073/pnas.1406218111 · 9.81 Impact Factor