Show simple item record

dc.contributor.authorSoghoian, Damien Zadouren_US
dc.date.accessioned2015-03-18T13:10:03Z
dash.embargo.terms2017-03-01en_US
dc.date.created2015-03en_US
dc.date.issued2015-01-15en_US
dc.date.submitted2015en_US
dc.identifier.citationSoghoian, Damien Zadour. 2015. HIV-Specific CD4 T Cells and Viral Control. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14226084
dc.description.abstractCD4 T cells play an important and central role in the immune system, coordinating the arms of the adaptive immune system to shape an effective response while simultaneously regulating non-essential or deleterious activities. Their critical necessity is demonstrated most strikingly during acquired immunodeficiency syndrome (AIDS), when depletion of CD4 T cells by human immunodeficiency virus (HIV) type 1 ultimately results in a host of immune dysfunctions and susceptibility to opportunistic pathogens. Although virus-specific CD4 T cell responses are generally vital for the control of viral infections, HIV-specific CD4 T cells have long been recognized to be preferentially targeted and depleted by the virus—raising questions about their utility as immune effectors both during HIV-1 infection and in the context of a prospective HIV-1 vaccine. However, more recent research has challenged the notion that HIV-specific CD4 T cells are only relevant as targets. There is a growing appreciation for the crucial role that these cells may play in mediating anti-HIV immunity through a diverse array of effector functions—including direct anti-viral cytotoxicity. Here we show that HIV-specific CD4 T cell responses are evident throughout the course of HIV disease, including acute infection. In particular, an expansion of HIV-specific CD4 T cells with cytolytic potential early after acute HIV infection is associated with lower viral set point and better clinical progression. This expansion is evident both as an increase in HIV-specific CD4 T cells able to degranulate upon antigen recognition and as cells with a unique granzyme and perforin expression pattern. Further, HIV-specific cytolytic CD4 T cell responses are functionally enhanced in the setting of durable HIV control during chronic infection, where they exhibit a profile reminiscent of HIV-specific CD8 T cells and are associated with T-bet and Eomesodermin expression. We also show that in HIV controllers, the function of HIV-specific CD4 T cells is very tightly correlated with clinical status. Together these results strongly support the concept that CD4 T cells are critical players in the cellular immune response to HIV, and point to specific CD4 T cell functions—including direct cytolysis—which may be most important for anti-HIV immunity.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoenen_US
dash.licenseLAAen_US
dc.subjectBiology, Virologyen_US
dc.titleHIV-Specific CD4 T Cells and Viral Controlen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorSoghoian, Damien Zadouren_US
dc.date.available2017-03-01T08:31:18Z
thesis.degree.date2015en_US
thesis.degree.grantorGraduate School of Arts & Sciencesen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
dc.contributor.committeeMemberPillai, Shiven_US
dc.contributor.committeeMemberKaur, Mitien_US
dc.contributor.committeeMemberLuban, Jeremyen_US
dc.type.materialtexten_US
thesis.degree.departmentMedical Sciencesen_US
dash.identifier.vireohttp://etds.lib.harvard.edu/gsas/admin/view/64en_US
dc.description.keywordsHIV; CD4 T-cells; flow cytometry; cytolytic T lymphocytesen_US
dash.author.emaildamien.soghoian@gmail.comen_US
dash.identifier.drsurn-3:HUL.DRS.OBJECT:25119283en_US
dash.contributor.affiliatedSoghoian, Damien


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record