Novel pathways of antigen presentation for the maintenance of memory

Gray, David; Kosco, Marie H.; Stockinger, Brigitta

doi:10.1093/intimm/3.2.141

Cited by 166 publications

(95 citation statements)

References 18 publications

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“…Additionally, with time, memory CD8 ϩ T cells shift progressively to the less-activated CD62L hi phenotype. Furthermore, if the putative ''persistent'' pMHCI complexes are thought to come from, say, antigen-antibody complexes on the surface of follicular DCs (27), it would be expected that proteins made in great abundance (like NP) should be more likely to persist at high levels than, say, the low abundance (28) acid polymerase (PA). What the evidence shows, though, is that the larger, antigendriven clonal expansions that result in a bigger CTL memory pool specific for D b NP 366 tend, with time, to converge in size to be more like those recognizing D b PA 224 (29).…”

Section: Discussionmentioning

confidence: 99%

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Mintern

Bedoui²,

Davey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Antigen expressed as MHC Class I glycoprotein (pMHCI) complexes on dendritic cells is the primary driver of CD8 ؉ T cell clonal expansion and differentiation. As we seek to define the molecular differences between acutely stimulated cytotoxic T lymphocyte (CTL) effectors and long-lived memory T cells, it is essential that we understand the duration of in vivo pMHCI persistence. Although infectious influenza A virus is readily cleared by mammalian hosts, that does not necessarily mean that all influenza antigen is totally eliminated. An exhaustive series of carefully controlled adoptive transfer experiments using 3 different carboxy fluorescein diacetate succinimidyl esterlabeled T cell receptor-transgenic CTL populations and a spectrum of genetically engineered and wild-type influenza A viruses provided no evidence for pMHCI persistence over the 30 -60-d interval after virus challenge. Molecular profiles identified in antigen-specific T cells at this time may thus be considered to reflect established immunologic memory and not recent CTL activation from a persistent pMHCI pool. V irus-specific CD8ϩ T cell-mediated immunity is a critical component of the host response. Naive CD8 ϩ T cells recognize virus-derived peptides presented in the context of MHC Class I glycoproteins (pMHCI). Encountering these pMHCI complexes on professional antigen-presenting cells (APCs) in draining lymph nodes (1) triggers CD8 ϩ T cell proliferation and differentiation (2, 3) to mediate cytotoxic T lymphocyte (CTL) effector function, a primary mechanism of virus clearance (4). Other clonally expanded CD8 ϩ T cells survive to establish a stable memory pool (2). Although it is possible to probe the molecular events that underlie these events using in vitro culture systems, what happens to T cells during and after an infectious challenge is optimally determined by minimizing the extent of manipulation after lymphocyte separation from the intact host. For example, we have recently demonstrated that a minority of influenza-specific memory CTLs recovered directly ex vivo can maintain cytotoxic gene expression for up to 1 year after infection (5). Understanding what this means in a molecular sense requires a clear picture of the likely stimulatory environment. Defining the importance of antigen load through the establishment and maintenance phases of CD8ϩ T cell immunity is also essential if we are to take rational approaches to vaccine design.Some viruses that first establish an acute, lytic infectious process have evolved mechanisms that allow them to persist at a low level (or in a latent form) for the life of the host. This is not the case for influenza in immunologically competent mice or, so far as we are aware, in other mammalian species. Numerous lines of evidence based on (i) feeding the thymidine analogue bromodeoxyuridine to monitor antigen-specific T cell expansion (6), (ii) isolating dendritic cells (DCs) to probe for pMHCI expression (7), and (iii) PCR to detect viral genome in the recovered lung (8-10) support the view that the...

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Section: Discussionmentioning

confidence: 99%

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Mintern

Bedoui²,

Davey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…This cellular composition resembles that of lymphoid follicles seen in lymph nodes [36]. Follicular dendritic cells in the centre of lymphoid follicles and interdigitating cells in the peripheral area of lymphoid follicles may serve to present a viral antigen to B cells, CD4 þ T cells, and CD8 þ T cells [37][38][39]. Our immunohistochemical study parallels these findings, and strongly supports the hypothesis that intraportal lymphoid follicles in chronic hepatitis C behave as true functional lymphoid follicles, in which presentation of HCV-related antigens to naive B and T lymphocytes and the transition from naive lymphocytes to the memory phenotype may occur.…”

Section: Discussionmentioning

confidence: 99%

Naive and memory T cell infiltrates in chronic hepatitis C: phenotypic changes with interferon treatment

Imada

Fukuda

Koyama

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe phenotypes of infiltrating lymphocytes in liver with chronic hepatitis C, including changes associated with interferon (IFN) treatment, were characterized. Specimens obtained from 22 patients treated with IFN were examined using avidin-biotin-peroxidase immunohistochemistry. In areas of lobular and periportal inflammation, most lymphocytes were CD8 þ T cells of the CD45RO þ (memory) subset. The centres of lymphoid follicles were occupied by CD20 þ B cells and a few CD4 þ T cells which were CD45RA þ (naive subset). Follicular centres were surrounded mainly with CD4 þ T cells. CD8 þ T cells, mostly CD45RO þ , were scattered through the mantle zones of follicles and extended around them. No significant changes in CD45RA þ lobular infiltrates accompanied IFN treatment. On the other hand, the number of CD45RO þ lobular infiltrates decreased after IFN treatment in complete responders (P < 0 . 01). Moreover, there were significant correlations between CD45RO þ cell counts and serum alanine aminotransferase concentrations, CD45RO þ cell counts and the liver histologic grade and CD45RO þ cell counts and CD8 þ cell counts. These results suggest that CD8 þ memory T cells participate in hepatocyte injury in chronic hepatitis C, and that a decrease of CD8 þ memory T cells correlates with the decreased liver inflammation with IFN treatment.

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“…These showed little labelling and were termed ' oligosynthetic ', while the mesenteric and deep cervical nodes, which contained many more labelled cells, were termed ' polysynthetic '. Although recent studies have firmly established that the major function of the germinal centres is to generate memory B lymphocytes (Klaus et al 1980 ;Kroese et al 1987b ;Gray, 1988 ;Gray et al 1991 ;Liu et al 1991Liu et al , 1997Nieuwenhuis et al 1992 ;MacLennan, 1994), the precise functional significance of primary follicles remains to be defined. The mechanism underlying the formation of lymph follicles also remains unclear.…”

Section: mentioning

confidence: 99%

Patterns of age‐dependent changes in the numbers of lymph follicles and germinal centres in somatic and mesenteric lymph nodes in growing C57Bl/6 mice

et al. 2001

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The timing of the first appearance of lymph follicles and germinal centres in various lymph nodes, and the ways in which numbers of these and IgM-synthesising cells increase within the nodes, were investigated in male and female C57Bl\6N mice aged from 4 d to 16 wk. The lymphoid organs examined were the Peyer's patches, spleen, somatic (submandibular, deep cervical, brachial, axillary, inguinal and popliteal) and visceral (mesenteric and lumbar) lymph nodes. Primary follicles appeared in most somatic lymph nodes 6 d after birth. The number of follicles per node then increased rather sharply in larger lymph nodes and slowly in smaller nodes, up to 28 d of age, reaching a level which varied according to the location of the node. Thereafter, the number of follicles in the somatic lymph nodes increased only slightly to moderately, reaching a peak or plateau at 8-12 wk. In the mesenteric (ileocaecal) nodes, primary follicles first appeared at 12 d, then increased linearly during the suckling period and after weaning to reach a plateau at 8 wk of age. Germinal centres appeared in the submandibular and mesenteric nodes at 28 d and their numbers increased consistently in the latter, while remaining low in the former. The impact of possible ' natural ' exogenous antigen stimulation of the various lymph nodes was estimated from the presence of IgMsynthesising cells and germinal centres. Differences between the patterns of age-dependent changes in the numbers of lymph follicles observed in the somatic and mesenteric lymph nodes during their ontogeny are discussed in relation to differences in the magnitude of the exogenous antigen stimulatory effect. We also found that the variations in the numbers of lymph follicles produced in somatic lymph nodes at different locations during the first 28 d after birth reflected differences in the dimensions of the body regions drained by a particular somatic lymph node at this stage of development.

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Novel pathways of antigen presentation for the maintenance of memory

Cited by 166 publications

References 18 publications

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Naive and memory T cell infiltrates in chronic hepatitis C: phenotypic changes with interferon treatment

Patterns of age‐dependent changes in the numbers of lymph follicles and germinal centres in somatic and mesenteric lymph nodes in growing C57Bl/6 mice

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