Impaired Development and Expansion of Germinal Center Follicular Th Cells in Simian Immunodeficiency Virus–Infected Neonatal Macaques
| Autor: | Xiaolei Wang, Lara A. Doyle-Meyers, Jiasheng Shao, Huanbin Xu, Kasi E. Russell-Lodrigue, Ronald S. Veazey, Marion S. Ratterree, Widade Ziani |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cellular differentiation Immunology Simian Acquired Immunodeficiency Syndrome HIV Infections Viremia Biology Lymphocyte Activation medicine.disease_cause Article Proinflammatory cytokine 03 medical and health sciences Immune system Immunity Paracrine Communication medicine Animals Humans Immunology and Allergy B cell Cell Proliferation B-Lymphocytes HIV virus diseases Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer Simian immunodeficiency virus Germinal Center medicine.disease Macaca mulatta Immunity Humoral Disease Models Animal 030104 developmental biology medicine.anatomical_structure Animals Newborn Simian Immunodeficiency Virus Lymph Nodes Immunologic Memory |
| Zdroj: | The Journal of Immunology. 201:1994-2003 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1800235 |
| Popis: | Germinal center (GC) CD4+ follicular Th (Tfh) cells are critical for cognate B cell help in humoral immune responses to pathogenic infections. Although Tfh cells are expanded or depleted in HIV/SIV-infected adults, the effects of pediatric HIV/SIV infection on Tfh cells remain unclear. In this study, we examined changes in lymphoid follicle formation in lymph nodes focusing on GC Tfh cells, B cell development, and differentiation in SIV-infected neonatal rhesus macaques (Macaca mulatta) compared with age-matched cohorts. Our data showed that follicles and GCs of normal infants rapidly formed in the first few weeks of age, in parallel with increasing GC Tfh cells in various lymphoid tissues. In contrast, GC development and GC Tfh cells were markedly impaired in SIV-infected infants. There was a very low frequency of GC Tfh cells throughout SIV infection in neonates and subsequent infants, accompanied by high viremia, reduction of B cell proliferation/resting memory B cells, and displayed proinflammatory unresponsiveness. These findings indicate neonatal HIV/SIV infection compromises the development of GC Tfh cells, likely contributing to ineffective Ab responses, high viremia, and eventually rapid disease progression to AIDS. |
| Databáze: | OpenAIRE |
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