Protective immunity towards intracellular pathogens

ArticleinCurrent Opinion in Immunology 18(4):458-64 · September 2006with8 Reads
DOI: 10.1016/j.coi.2006.05.008 · Source: PubMed
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.
    • "As a consequence, they are regarded as powerful mediators of immune protection from reinfection. In keeping with this, protective immunity by CD8 + memory T cells has been demonstrated in various experimental models of systemic infection, such as Listeria monocytogenes , lymphocytic choriomeningitis virus (LCMV), and the malaria parasite Plasmodium berghei (Bachmann et al., 1997Bachmann et al., , 2005 Wherry et al., 2003; Badovinac et al., 2005; Huster et al., 2006; Schmidt et al., 2008). Importantly, T cell immunity in these cases of systemic infection is long-lived and can be conferred to naïve animals by the adoptive transfer of pathogenspecific CD8 + memory T cells (Lau et al., 1994). "
    [Show abstract] [Hide abstract] ABSTRACT: Microbial infection primes a CD8(+) cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8(+) T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103(+) memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (T(RM)) in epithelial and neuronal tissues. We further discuss the role of T(RM) cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.
    Full-text · Article · Nov 2012
    • "T EMC preferentially home to peripheral tissues and respond to antigen encounter with immediate effector function but poor numeric expansion [41]. In contrast, T CMC home to lymphoid organs, can vigorously expand upon antigen reencounter and are therefore potentially assigned to the crucial T cell population that confers long-lasting protective immunity against microbial pathogens [42]. However, proliferative capacity does not necessarily correlate with protection against infection, since T CMC -like CD8 T cells induced by vaccination with heat-killed L. monocytogenes reveal vigorous proliferation and expansion after challenge with live Listeria, but do not protect against listeriosis as determined by clearance of the bacteria [43]. "
    [Show abstract] [Hide abstract] ABSTRACT: The Salmonella type III secretion system (T3SS) efficiently translocates heterologous proteins into the cytosol of eukaryotic cells. This leads to an antigen-specific CD8 T-cell induction in mice orally immunized with recombinant Salmonella. Recently, we have used Salmonella's T3SS as a prophylactic and therapeutic intervention against a murine fibrosarcoma. In this study, we constructed a recombinant Salmonella strain translocating the immunogenic H-2D(b)-specific CD8 T-cell epitope VILTNPISM (KDR2) from the murine vascular endothelial growth factor receptor 2 (VEGFR2). VEGFR2 is a member of the tyrosine protein kinase family and is upregulated on proliferating endothelial cells of the tumor vasculature. After single orogastric vaccination, we detected significant numbers of KDR2-tetramer-positive CD8 T cells in the spleens of immunized mice. The efficacy of these cytotoxic T cells was evaluated in a prophylactic setting to protect mice from challenges with B16F10 melanoma cells in a flank tumor model, and to reduce dissemination of spontaneous pulmonary melanoma metastases. Vaccinated mice revealed a reduction of angiogenesis by 62% in the solid tumor and consequently a significant decrease of tumor growth as compared to non-immunized mice. Moreover, in the lung metastasis model, immunization with recombinant Salmonella resulted in a reduction of the metastatic melanoma burden by approximately 60%.
    Full-text · Article · Apr 2012
    • "Historically, it had been difficult to demonstrate the presence of memory-versus effector-prone T cell subsets due to the fact that most known features of memory T cells were either uniformly expressed or uniformly absent from all T cells participating in primary responses to a given antigen [2] . However, further research yielded the identification of markers differentially expressed on responding T cells early after primary antigen contact, and it soon became obvious that, depending on the set of markers examined, T cell subsets differ with regard to their migratory activity, effector function, and future capacity to become memory cells [3]. The advent of major histocompatibility complex (MHC) multimer technology enabled the study of T cell populations of identical peptide–MHC specificity and confirmed aspects of diversification first observed in less rigidly controlled systems. "
    [Show abstract] [Hide abstract] ABSTRACT: During the past two decades of research in T cell biology, an increasing number of distinct T cell subsets arising during the transition from naïve to antigen-experienced T cells have been identified. Recently, it has been appreciated that, in different experimental settings, distinct T cell subsets can be generated in parallel within the same immune response. While signals driving a single "lineage" path of T cell differentiation are becoming increasingly clear, it remains largely enigmatic how the phenotypic and functional diversification creating a multi-faceted T cell response is achieved. Here, we review current literature indicating that diversification is a stable trait of CD8(+) T cell responses. We showcase novel technologies providing deeper insights into the process of diversification among the descendants of individual T cells, and introduce two models that emphasize either intrinsic noise or extrinsic signals as driving forces behind the diversification of single cell-derived T cell progeny populations in vivo.
    Full-text · Article · Apr 2012
Show more