Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells

Pepper, Marion; Linehan, Jonathan L.; Pagán, Antonio J.; Zell, Traci; Dileepan, Thamotharampillai; Cleary, P. Patrick; Jenkins, Marc K.

doi:10.1038/ni.1826

Cited by 254 publications

(316 citation statements)

References 57 publications

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“…After 120 days, antigen‐experienced CD4 + T lymphocytes were no longer detectable in spleen or lymph nodes, while in bone marrow, a stable population had been established 59. In contrast, the group of Jenkins described the preferential location of memory CD4 + T cells in the spleen and lymph nodes until day 160 after infection, in an immune response to Listeria monocytogenes infection 126. It should be noted, however, that from day 200 onwards, in that same figure, about equal numbers of antigen‐experienced CD4 + T cells were maintained in the bone marrow, as compared to the secondary lymphoid organs.…”

Section: The Bone Marrow—hub For Circulating or Home Of Resident Memomentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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Section: The Bone Marrow—hub For Circulating or Home Of Resident Memomentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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“…Th17 cells appear to be even less stable. Although it is now clear that in vitro generated Th17 cells and in vivo generated Th17 cells might be different in terms of developmental plasticity [154], it remains to be determined whether memory T cells that express a classic Th17 phenotype really exist [40]. Using reporter mouse/fate tracking systems, it has been shown that IL-17A or IL-17F producing T cells are reprogrammed to produce both IL-17 and IFN-c or IFN-c only in the spleen and within the CNS [155,156].…”

Section: Plasticity Of T Helper Cells In Eaementioning

confidence: 99%

Cytokines and effector T cell subsets causing autoimmune CNS disease

2011

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a b s t r a c tAlthough experimental autoimmune encephalomyelitis (EAE) is limited in its potency to reproduce the entirety of clinical and histopathologic features of multiple sclerosis (MS), this model has been successfully used to prove that MS like autoimmunity in the CNS is orchestrated by autoantigen specific T cells. EAE was also very useful to refute the idea that IFN-c producing T helper type 1 (Th1) cells were the sole players within the pathogenic T cell response. Rather, ''new'' T cell lineages such as IL-17 producing Th17 cells or IL-9 producing Th9 cells have been first discovered in the context of EAE. Here, we will summarize new concepts of early and late T cell plasticity and the cytokine network that shapes T helper cell responses and lesion development in CNS specific autoimmunity.

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“…Lymphocytes isolated from infected mice were incubated in a 96-well plate, at a concentration of 3 × 10 6 cells per well. Cells were incubated in the presence of ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] or Sendai HN [421][422][423][424][425][426][427][428][429][430][431][432][433][434][435][436] peptide (5 μg/mL each) for 2 h at 37°C; Brefeldin A (50 μg/mL) was added, and the incubation was continued for an additional 4 h. Surface staining for CD4, CD8, PD-1, and KLRG1 was performed, as described previously (22), and the cells were fixed and permeabilized using a Cytofix/Cytoperm Fixation/ Permeabilization kit (BD Biosciences). For detection of intracellular IFNγ and TNFα, the cells were incubated for 30 min in Perm/Wash Buffer (BD Biosciences) with anti-IFNγ (clone XMG1.2) and anti-TNFα (clone MP6-XT22); the cells were analyzed as described above.…”

Section: Methodsmentioning

confidence: 99%

Distinct functions of antigen-specific CD4 T cells during murineMycobacterium tuberculosisinfection

Reiley

Shafiani

Wittmer

et al. 2010

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

164

201

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The immune response elicited after Mycobacterium tuberculosis (Mtb) infection is critically dependent on CD4 T cells during both acute and chronic infection. How CD4 T-cell responses are maintained throughout infection is not well understood, and evidence from other infection models has suggested that, under conditions of chronic antigen stimulation, T cells can undergo replicative exhaustion. These findings led us to determine whether subpopulations of CD4 T cells existed that displayed markers of terminal differentiation or exhaustion during murine Mtb infection. Analysis of antigen-specific effector CD4 T cells revealed that programmed death-1 (PD-1) and the killer cell lectin-like receptor G1 (KLRG1) delineated subpopulations of T cells. PD-1-expressing CD4 T cells were highly proliferative, whereas KLRG1 cells exhibited a short lifespan and secreted the cytokines IFNγ and TNFα. Adoptive transfer studies demonstrated that proliferating PD-1-positive CD4 T cells differentiated into cytokine-secreting KLRG1-positive T cells, but not vice versa. Thus, proliferating PD-1-positive cells are not exhausted, but appear to be central to maintaining antigen-specific effector T cells during chronic Mtb infection. Our findings suggest that antigen-specific T-cell responses are maintained during chronic mycobacterial infection through the continual production of terminal effector cells from a proliferating precursor population.T uberculosis presents a challenging worldwide public heath problem. Infection with Mycobacterium tuberculosis (Mtb) elicits humoral and cellular immune responses that normally control bacterial burden. However, bacteria are seldom, if ever, eradicated, and control of the infection requires continual effector T-cell responses. Consequently, either the depletion or suppression of T-cell responses results in disease reactivation (1). In the mouse model, Mtb causes chronic infection and control of infection is maintained by T cells essentially indefinitely (2).Although a sustained T-cell response against Mtb infection is necessary, it is not understood how effector T cells are maintained. We have previously demonstrated that CD4 T-cell responses are associated with extensive proliferation throughout Mtb infection (3), suggesting that proliferation is a major mechanism required for the maintenance of T-cell responses. However, it is not clear how T-cell proliferation can be maintained during chronic infection, especially because effector T cells have been described to have a limited capacity for self-renewal (4).Although the numbers of antigen-specific T cells are relatively stable during chronic Mtb infection, CD4 T cells proliferate extensively, suggesting that a high turnover of effector CD4 T cells occurs. This high level of turnover suggests that effector T cells become exhausted or terminally differentiated, and that the maintenance of the T-cell response depends on the continual replacement of effector T cells. The expression of several cellsurface receptors has been correlated with functional e...

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Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells

Cited by 254 publications

References 57 publications

Immunological memories of the bone marrow

Immunological memories of the bone marrow

Cytokines and effector T cell subsets causing autoimmune CNS disease

Distinct functions of antigen-specific CD4 T cells during murineMycobacterium tuberculosisinfection

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