Browsing by Subject "Antigens"
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Item B Cell Modulation of T Cell Responses in Multiple Sclerosis(2010-01-12) Harp, Christopher Todd; Monson, Nancy L.Until recently, a definitive role for B cells in the pathogenesis of the autoimmune neurological disorder multiple sclerosis (MS), had not been widely accepted, and remains poorly understood. B cells have multiple functions in the immune system and can both positively and negatively modulate immune responses through the production of antibody, cytokine secretion, and/or antigen presentation. Several studies indirectly suggest that B cell-T cell cooperation may be paramount in MS disease pathogenesis, although this interaction has not been well studied in MS. Therefore, the focus of my thesis project was to test the hypothesis that B cells could be efficient neuro-antigen presenting cells in the context of MS. My work has demonstrated that the cerebrospinal fluid (CSF) B cell population in MS shows characteristics of both auto-reactivity and antigen driven selection in a germinal center reaction. These findings suggest that neuro-antigen driven selection had occurred in the periphery and prompted investigation of B cells as neuro-antigen presenting cells. Examination of CD40 ligand (CD40L) and interleukin-4 (IL-4) activated peripheral B cells demonstrated for the first time that B cells could efficiently elicit myelin basic protein (MBP) specific CD8+ and CD4+ T cell proliferation from resting T cells in vitro through a mechanism that was partially dependent on presentation through HLA-DR. Further inquiry into the antigen presentation capacity of specific subpopulations of resting B cells revealed that memory B cells from MS patients (but not healthy donors (HDs)) were significantly better neuro-antigen specific presenting cells than their na?ve counter parts. This data indicated that a specific peripheral immune response had been generated in response to neuro-antigens in RRMS patients but not HDs. Taken together, these data provide a model where antigen experienced peripheral B cells from MS patients (but not HDs) provide important T cell support through antigen presentation and add to our understanding of the role of B cells in the pathogenesis of this autoimmune disease of the CNS.Item Role of Nlc Cells in Murine Models of T Cell-Dependent Responses(2007-12-17) Jennings, Paula Alessandra; Yuan, DorothyNK cells are part of the innate immune system, yet they can also modulate the acquired immune response. Activated NK cells, for instance, can increase antigen specific IgG2a production in response to T independent responses, mostly through IFN-gamma secretion. Previous experiments examining the effect of NK cells on T cell- dependent antigens in various laboratories have yielded inconsistent conclusions. Therefore attempts were made to further investigate this question. Whereas depletion of NK cells had no detectable effect on the response to a TD antigen in Ribi adjuvant injected intraperitoneally, the secondary IgG1 response can be significantly reduced. This result suggested a role for NK cells on the generation of memory T cells. Therefore experiments were initiated to investigate the effect of NK cells on T cell proliferation. The absence of NK cells during immunization was found to reduce primary T cell proliferation. Such effect was not observed when B cell antigen presentation was absent, which is known to be important for memory T cell generation. A direct effect of NK cells on B cell antigen presentation was assessed in vitro. These experiments showed that NK cells can upregulate B cell antigen presentation of ovalbumin to na?T cells expressing a transgene specific to the ovalbumin derived peptide, OVAp. This increase is contact dependent and can occur in the absence of IFN-gamma . Moreover, the NK cell enhancement of B cell presentation of intact protein was greater than the presentation of OVAp, which requires no processing. These experiments suggest that the upregulation involves both processing and presentation of antigen. These experiments show that NK cells have a direct effect on B cell antigen presentation and provide a mechanistic basis for the role of NK cells in modulating in vivo T cell- dependent antibody responses.Item [Southwestern News](2005-07-14) Rian, RussellItem Superantigens - fancy pathogens, or passing fancy?(1993-03-18) Karp, David R.Item [UT Southwestern Medical Center News](2009-08-10) Rian, Russell