Immune reconstitution after hematopoietic cell transplantation
Abstract/Contents
- Abstract
- Infections resulting from poor immunity remain a major complication after hematopoietic cell transplantation (HCT) and this thesis focuses on two main aspects of immune reconstitution post-HCT. First, the role of adoptively transferred mature donor cells in supplementing immunity is addressed. We report that, while animals receiving whole bone marrow transplants have higher levels of immune cells in the blood and no overt manifestations of clinical illness, there is reduced lymph node cellularity after allogeneic transplantation, destruction of lymph node architecture after fully MHC-disparate transplant and poor proliferative responses to a novel antigen. We conclude that the problems associated with subclinical graft-versus-host disease outweigh any benefits of adoptive transfer of mature cells in this setting. The second main area of investigation focuses on the ability of T cells to provide help to donor B cells and induce antibody production to T-dependent antigens after purified hematopoietic stem cell transplant (HSCT). We report that antibody production to a T-dependent antigen is limited to host B cells in fully MHC-disparate chimeras until 12 weeks post-transplant. In contrast, donor and host-derived B cells produce antibody to a T-independent antigen at six weeks in all chimeras studied and to a T-dependent antigen in MHC-matched and haploidentical chimeras where donor and host share an MHC allele. This delayed reconstitution of cells able to provide help to B cells presenting only donor MHC occurs despite the functional development of donor-derived T-Follicular Helper cells, the subset of T cells believed to provide B cell help, at 6 weeks post-HSCT. These data suggest that reconstitution of donor-restricted T cell function may be delayed in fully MHC-disparate hematopoietic chimeras. However, functional donor-restricted responses do eventually develop in the absence of any graft-versus-host disease. We believe that these findings provide important insights into immune reconstitution after MHC-disparate HSCT, and suggest that graft-versus-host disease rather than MHC-disparity may be the major obstacle to immune function after HCT. This work also provides important insights into the function and development of T-Follicular Helper cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Linderman, Jessica Ashley |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Shizuru, Judith Anne |
| Thesis advisor | Shizuru, Judith Anne |
| Thesis advisor | Mellins, Elizabeth |
| Thesis advisor | Miklos, David (David B.) |
| Thesis advisor | Robinson, William (William Hewitt) |
| Thesis advisor | Weissman, Irving L |
| Advisor | Mellins, Elizabeth |
| Advisor | Miklos, David (David B.) |
| Advisor | Robinson, William (William Hewitt) |
| Advisor | Weissman, Irving L |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jessica Ashley Linderman. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Jessica Ashley Linderman
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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