Impact of Time on the Size, Shape and Effector Responses of Cd4⁺ T Cells

Persistent Link:
http://hdl.handle.net/10150/556850
Title:
Impact of Time on the Size, Shape and Effector Responses of Cd4⁺ T Cells
Author:
Deshpande, Neha Rajendra
Issue Date:
2015
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release after 4-May-2017
Abstract:
T cells discriminate self from foreign peptides presented in the context of self-major histocompatibility complex (pMHC) molecules via clonotypic T cell receptors (TCRs). CD8⁺ T cell recognition and responsiveness to foreign pMHC is known to diminish over the lifespan, which is consistent with gradual thymic involution over time. It is further supported by experimental evidence that restricting the diversity of class I MHC peptides during positive and negative selection results in selection of fewer CD8⁺ T cells that are highly specific for pMHC. How the affinity of the CD4⁺ T cell compartment for self-pMHC, and its capacity to bind foreign-pMHC change over the lifespan are fundamental aspect of T cell biology that remain largely unexplored. Experimentally restricting thymic selection is known to allow degenerate CD4⁺ T cells to develop. This suggests that they might accumulate in the CD4⁺ T cell compartment over time. We report that, while old mice (18-22 months) contain fewer CD4⁺ T cells than adults (8-12 weeks), those that remain have a higher intrinsic affinity for self-pMHC. Old mice also have more cells that bind distinct foreign-pMHCs, either alone or in combination. The numerical increase of these subsets with age directly correlates with their affinity for self-pMHC. However, no relationship was observed between affinity for self-pMHC and responsiveness to foreign-pMHC. These data demonstrate that the CD4⁺ T cell compartment preferentially accumulates promiscuous constituents with age as a consequence of higher affinity T cell receptor interactions with self-pMHC. These results have important implications for the design of immunotherapeutics targeting CD4⁺ T cells to improve immunity in older adults.
Type:
text; Electronic Dissertation
Keywords:
Immunobiology
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Immunobiology
Degree Grantor:
University of Arizona
Advisor:
Kuhns, Michael S.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleImpact of Time on the Size, Shape and Effector Responses of Cd4⁺ T Cellsen_US
dc.creatorDeshpande, Neha Rajendraen
dc.contributor.authorDeshpande, Neha Rajendraen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.releaseRelease after 4-May-2017en
dc.description.abstractT cells discriminate self from foreign peptides presented in the context of self-major histocompatibility complex (pMHC) molecules via clonotypic T cell receptors (TCRs). CD8⁺ T cell recognition and responsiveness to foreign pMHC is known to diminish over the lifespan, which is consistent with gradual thymic involution over time. It is further supported by experimental evidence that restricting the diversity of class I MHC peptides during positive and negative selection results in selection of fewer CD8⁺ T cells that are highly specific for pMHC. How the affinity of the CD4⁺ T cell compartment for self-pMHC, and its capacity to bind foreign-pMHC change over the lifespan are fundamental aspect of T cell biology that remain largely unexplored. Experimentally restricting thymic selection is known to allow degenerate CD4⁺ T cells to develop. This suggests that they might accumulate in the CD4⁺ T cell compartment over time. We report that, while old mice (18-22 months) contain fewer CD4⁺ T cells than adults (8-12 weeks), those that remain have a higher intrinsic affinity for self-pMHC. Old mice also have more cells that bind distinct foreign-pMHCs, either alone or in combination. The numerical increase of these subsets with age directly correlates with their affinity for self-pMHC. However, no relationship was observed between affinity for self-pMHC and responsiveness to foreign-pMHC. These data demonstrate that the CD4⁺ T cell compartment preferentially accumulates promiscuous constituents with age as a consequence of higher affinity T cell receptor interactions with self-pMHC. These results have important implications for the design of immunotherapeutics targeting CD4⁺ T cells to improve immunity in older adults.en
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectImmunobiologyen
thesis.degree.namePh.D.en
thesis.degree.leveldoctoralen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineImmunobiologyen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorKuhns, Michael S.en
dc.contributor.committeememberNikolich-Zugich, Jankoen
dc.contributor.committeememberGoodrum, Feliciaen
dc.contributor.committeememberLybarger, Lonnieen
dc.contributor.committeememberSo, Magdaleneen
dc.contributor.committeememberKuhns, Michael S.en
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.