Compromised steady‐state germinal center activity with age in nonhuman primates
| Autor: | Francois Villinger, Tirupataiah Sirupangi, Rajendra Pahwa, Lucio Gama, Kimberly Shankwitz, Kyle Blaine Russel, Constantinos Petrovas, Suresh Pallikkuth, Savita Pahwa, Richard A. Koup, Daniel Kvistad, Li Pan |
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| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Aging medicine.medical_specialty Cell CD8-Positive T-Lymphocytes Biology Positive correlation Monocytes law.invention 03 medical and health sciences follicles 0302 clinical medicine Immune system Antigens CD law Internal medicine Follicular phase medicine Animals Cytotoxic T cell Inflammation B-Lymphocytes Original Paper B cells Germinal center Forkhead Transcription Factors Cell Biology Germinal Center Macaca mulatta Lymphocyte Activation Gene 3 Protein Original Papers Immunity Humoral 030104 developmental biology Endocrinology medicine.anatomical_structure Suppressor Lymph Nodes Steady state (chemistry) Tfh cells 030217 neurology & neurosurgery Granulocytes |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| Popis: | Age‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging. Steady‐state germinal center immune reactivity is compromised in aged NHPs. This loss of reactivity is characterized by changes in many GC associated cell populations including Tfh, B cells, and follicular Tregs. |
| Databáze: | OpenAIRE |
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