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Search Results to Susan L Swain PhD

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CD4 T cell memory. We can generate in vitro CD4 T cells that are for all extents and purposes identical to the memory CD4 T cells observed in vivo. In situ memory CD4 T cells persist at very low frequency and in most instances it is difficult to analyze them thoroughly using tetramer or multimer reagents both because of their low frequency and the relatively low specific affinity of the Class II reagents for the TcR. Being able to generate “recent” memory cells in vitro gives us the opportunity to analyze in detail the mechanisms by which memory CD4 T cells may contribute to secondary immunity and immune protection. Once identified. will determine if particular pathways are relevant in situ. We have discovered that memory CD4 T cells are superior in protection to those from the primary response and that they display pleitropic functions that have not been previously identified.

Cytotoxic CD4 Effectors. One unexpected function of CD4 T cells we identified is robust, perforin-dependent cytotoxic activity (7, 16). Cytotoxic activity by CD4 T cells has been reported in response to several infections, but its significance has not heretofore been established. We find that “Th1 polarized” CD4 effectors and more relevantly the CD4 effectors found in the lung following influenza infection, are able to kill infected or peptide-pulsed Class II-bearing targets and we find that this perforin dependent activity can work together with antibody to provide protection against lethal influenza challenge in otherwise unprimed mice (17). We also will determine when memory CD4 T cells re-express cytotoxic activity following in vivo challenge and how cytotoxic killing contributes to the memory cell mediated protection. We want to analyze how the program of cytotoxicity is induced in these “ThCTL”.

Memory CD4 Cells Enhance an Innate Response. Memory cells can act by becoming secondary effectors but they are best characterized by their ability respond rapidly even to low antigen doses, by producing cytokines and chemokines and it is assumed that these initial abilities are key to memory cell activity. However this assumption has not been directly demonstrated and the mechanisms involved and how they might contribute to immunity have not been elucidated. We find that restimulation of memory CD4 T cells leads to a markedly enhanced early innate response to influenza infection both in the lung and systemically (17). This response peaks 2-3 days after infection and is transient. We see enhanced production of IL-6 locally and systemically and enhanced production a broad spectrum of innate inflammatory mediators in the lung. We hope to determine in detail the pathways leading to optimum memory T cell-induced innate responses. We suggest a concurrent activation of CD4 memory cells may be an effective adjuvant for vaccination and will be testing this hypothesis as well as mechanisms that lead to viral control over the next couple of years.

Aging and Immunity: The study of the impact of aging on CD4 T cell function at the naïve and memory stages has lead us to better understanding of fundamental aspects of T cell behavior in addition to providing important information about what vaccine approaches are most likely to be successful for the aged.

Nature of CD4 Aging “Defects”. We have identified multiple levels at which aged naïve CD4 T cells are defective including initial early response to TcR triggering, IL-2 production, expansion and effector generation. The defects in helper function and in the 20 response of memory cells generated from aged naïve CD4 T cells are particularly dramatic. In recent studies we have recapitulated memory age-associated defects in recently generated memory cells in vitro (23). In vitro aged memory cells are markedly defective in production of particular cytokines, IL-4, IL-5 and IL-2, while others are little affected (IFNg, IL-10, TNF), suggesting the aging “defect” may be restricted to loss of potential to make certain CD4 T cell subsets, such as those responsible for help to B cells .We will pursue this hypothesis both in vitro and in vivo.

We have found that aged naïve CD4 T cells are in fact longer-lived than their naïve counterparts (23). We find that reduced expression of Bim, a proapoptotic protein, is responsible for this increase in lifespan and that the increase in lifespan is required for the development of aging defects. We are now investigating the factors that regulate Bim expression.

Enhancement by Inflammatory Cytokines. We have shown that the defective effector generation responses of naïve CD4 T cells from aged animals can be overcome by IL-2 and by proinflammatory cytokines, in particular a mix of IL-1, IL-6 and TNF (20,21). We want to determine the extent to which the inflammatory cytokines can reverse the heritable aging defects and restore functional memory generation. We have developed in vitro models to test the generation of effectors and memory. In these models we are evaluating TLR agonists for their ability to restore aged naïve CD4 responses to peptide-pulsed derived dendritic cells (DC). Pre-incubation of DC with many TLR agonists, enhances expansion of the responding aged naïve CD4 T cells via a mechanism dependent on IL-6 that acts in part by increasing survival of the developing effector population. We plan to use this model to identify the extent of the rescue and what pathways and mechanisms contribute with the ultimate goal of evaluating whether specific TLR stimulation or stimulation of specific pathways might improve the response of the elderly to vaccines. We want to see if we can reproduce this model with human naïve CD4 T cells and DC derived from peripheral blood and if TLR agonists can also enhance those responses.


One or more keywords matched the following items that are connected to Swain, Susan

Item TypeName
Academic Article Enhanced development of Th2-like primary CD4 effectors in response to sustained exposure to limited rIL-4 in vivo.
Academic Article Regulation of CD40 ligand expression on naive CD4 T cells: a role for TCR but not co-stimulatory signals.
Academic Article TCR triggering of anergic CD4 T cells in murine AIDS induces apoptosis rather than cytokine synthesis and proliferation.
Academic Article Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements.
Academic Article Analysis of CD4+ T cells that provide contact-dependent bystander help to B cells.
Academic Article Age-related changes in CD4 T cells of T cell receptor transgenic mice.
Academic Article CD4 T cell anergy in murine AIDS: costimulation via CD28 and the addition of IL-12 are not sufficient to rescue anergic CD4 T cells.
Academic Article From naive to effector--alterations with aging.
Academic Article Long-term CD4+ memory T cells from the spleen lack MEL-14, the lymph node homing receptor.
Academic Article Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice.
Academic Article The defects in effector generation associated with aging can be reversed by addition of IL-2 but not other related gamma(c)-receptor binding cytokines.
Academic Article Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals.
Academic Article Transcriptional repression of the IL-2 gene in Th cells by ZEB.
Academic Article B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity.
Academic Article High antigen density and IL-2 are required for generation of CD4 effectors secreting Th1 rather than Th0 cytokines.
Academic Article CD4 effector T cell subsets in the response to influenza: heterogeneity, migration, and function.
Academic Article Role of T cells in the B-cell response: glutaraldehyde-fixed T-helper hybridoma cells synergize with the lymphokine IL-4 to induce B-cell activation and proliferation.
Academic Article CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly.
Academic Article Lymphokines and the immune response: the central role of interleukin-2.
Academic Article IL-7: maintaining T-cell memory and achieving homeostasis.
Academic Article IL-4 directs the development of Th2-like helper effectors.
Academic Article Environmental and intrinsic factors lead to antigen unresponsiveness in CD4(+) recent thymic emigrants from aged mice.
Academic Article IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge.
Academic Article Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells.
Academic Article Interleukin 18: tipping the balance towards a T helper cell 1 response.
Academic Article IL-2 receptor (Tac antigen) protein expression is down-regulated by the 5'-untranslated region of the mRNA.
Academic Article Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge.
Academic Article IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge.
Academic Article T-cell immunosenescence: lessons learned from mouse models of aging.
Academic Article Role of antigen in the B cell response. Specific antigen and the lymphokine IL-5 synergize to drive B cell lymphoma proliferation and differentiation to Ig secretion.
Academic Article Stimulation of gut-associated lymphoid cells by IL-4 and B-cell growth factor II.
Academic Article Characterization of antigen-specific CD4+ effector T cells in vivo: immunization results in a transient population of MEL-14-, CD45RB- helper cells that secretes interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma.
Academic Article T-cell factors that promote B-cell proliferation and differentiation.
Academic Article Role of BCGFII in the differentiation to antibody secretion normal and tumor B cells.
Academic Article Krüppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation.
Academic Article Transforming growth factor-beta and IL-4 cause helper T cell precursors to develop into distinct effector helper cells that differ in lymphokine secretion pattern and cell surface phenotype.
Academic Article Effect of age on naive CD4 responses: impact on effector generation and memory development.
Academic Article Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors.
Academic Article The biological outcome of CD40 signaling is dependent on the duration of CD40 ligand expression: reciprocal regulation by interleukin (IL)-4 and IL-12.
Academic Article Characterization of T helper 1 and 2 cell subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production are present as precursors that require priming before they develop into lymphokine-secreting cells.
Academic Article B cell surface glycoprotein induced during growth response: molecular structure and expression pattern.
Academic Article Purification and partial sequence analysis of murine B cell growth factor II (interleukin 5).
Academic Article B cell response to fresh and effector T helper cells. Role of cognate T-B interaction and the cytokines IL-2, IL-4, and IL-6.
Academic Article Monoclonal antibody to L3T4 blocks the function of T cells specific for class 2 major histocompatibility complex antigens.
Academic Article Immunosuppressive ATS. V. Analysis of the effect of anti-thymocyte serum on T lymphocyte subsets.
Academic Article Induction of B cell differentiation by T cell factors. I. Stimulation of IgM secretion by products of a T cell hybridoma and a T cell line.
Academic Article IL-7 promotes the transition of CD4 effectors to persistent memory cells.
Academic Article T cell replacing factors in the B cell response to antigen.
Academic Article Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin.
Academic Article IL4 dictates T-cell differentiation.
Academic Article Distinct lymphokine production by CD4+ T cells isolated from mucosal and systemic lymphoid organs.
Academic Article Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells.
Academic Article Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen.
Academic Article Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo.
Academic Article Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen.
Academic Article CD4+ T cell subsets. Lymphokine secretion of memory cells and of effector cells that develop from precursors in vitro.
Academic Article Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection.
Academic Article Regulation of the IgM and IgA anti-dextran B1355S response: synergy between IFN-gamma, BCGF II, and IL 2.
Academic Article IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells.
Academic Article Regulation of CD4+ T-cell contraction during pathogen challenge.
Academic Article TLR-activated dendritic cells enhance the response of aged naive CD4 T cells via an IL-6-dependent mechanism.
Academic Article Regulation of isotype production by IL-4 and IL-5. Effects of lymphokines on Ig production depend on the state of activation of the responding B cells.
Academic Article The role of IL4 and IL5: characterization of a distinct helper T cell subset that makes IL4 and IL5 (Th2) and requires priming before induction of lymphokine secretion.
Academic Article B cell growth factor interactions.
Academic Article Interleukin 5 and interleukin 4 produced by Peyer's patch T cells selectively enhance immunoglobulin A expression.
Academic Article B cell stimulatory factor 1 (interleukin 4) is sufficient for the proliferation and differentiation of lectin-stimulated cytolytic T lymphocyte precursors.
Academic Article Regulation of the immune response T-cell interactions.
Academic Article Xenogeneic human anti-mouse T cell responses are due to the activity of the same functional T cell subsets responsible for allospecific and major histocompatibility complex-restricted responses.
Academic Article Lymphokine-mediated activation of a T cell-dependent IgA antipolysaccharide response.
Academic Article Evidence for two distinct activation states available to B lymphocytes.
Academic Article Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays.
Academic Article Partial purification and characterization of a BCGFII from EL4 culture supernatants.
Academic Article Culture supernatants of a stimulated T-cell line have helper activity that acts synergistically with interleukin 2 in the response of B cells to antigen.
Academic Article A monoclonal T cell-replacing activity can act directly on B cells to enhance clonal expansion.
Academic Article Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.
Academic Article Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines.
Academic Article Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response.
Academic Article The cytokines IL-4, IFN-gamma, and IL-12 regulate the development of subsets of memory effector helper T cells in vitro.
Academic Article Control of CD4 effector fate: transforming growth factor beta 1 and interleukin 2 synergize to prevent apoptosis and promote effector expansion.
Concept Interleukin-21 Receptor alpha Subunit
Concept Interleukin-10
Concept Interleukin-13
Concept Receptors, Interleukin-2
Concept Interleukin-7 Receptor alpha Subunit
Concept Interleukin-23
Concept Interleukin-5
Concept Interleukin-7
Concept Interleukin-2
Concept Interleukin-1
Concept Receptors, Interleukin-7
Concept Interleukin-17
Concept Interleukin-12 Subunit p40
Concept Interleukin-4
Concept Interleukin-6
Concept Receptors, Interleukin
Concept Interleukin-18
Concept Interleukin-12
Concept Interleukin-3
Academic Article CD4 T cell defects in the aged: causes, consequences and strategies to circumvent.
Academic Article Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2.
Academic Article IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age.
Academic Article Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection.
Academic Article IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells.
Academic Article Direct IL-6 Signals Maximize Protective Secondary CD4 T Cell Responses against Influenza.
Academic Article IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans.
Academic Article IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.
Academic Article IL-15 supports the generation of protective lung-resident memory CD4 T cells.
Academic Article Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation.

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