High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults

Frontiers in Immunology

Pieter Jooste¹  Warren Kuhn²  Thumbi Ndung'u⁴  Alasdair Leslie⁴  Lynn Morris⁷  Penny L. Moore⁷  Henrik Kløverpris⁸  Abigail Ngoepe⁹  Duran Ramsuran⁹  Farina Karim⁹  Alex K. Shalek^1,10  Toby Aicher^1,10  Samuel W. Kazer^1,10  Julia Roider^1,12  Emily Adland^1,13  Philip Goulder^1,15  Maximilian Muenchhoff^1,16  Takashi Maehara^1,17  Shiv Pillai^1,17 

[1] 0Paediatric Department, Kimberley Hospital, Kimberley, South Africa;1Department of Otorhinolaryngology, Stanger Hospital, KwaZulu-Natal, South Africa;2Max Planck Institute for Infection Biology, Berlin, Germany;3Department of Infection and Immunity, University College London, London, United Kingdom;4Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa;5Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;6Center for the AIDS Programme of Research in South Africa, Durban, South Africa;7Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa;Broad Institute of MIT and Harvard, Cambridge, MA, United States;Department of Chemistry and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Infectious Diseases, Medizinische Klinik IV, Ludwig-Maximilians-University Munich, Munich, Germany;Department of Paediatrics, Peter Medawar Building for Pathogen Research, Oxford University, Oxford, United Kingdom;Department of Virology, Max von Pettenkofer Institute, Ludwig-Maximilians-University Munich, Munich, Germany;HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa;Partner Site Munich, German Center for Infection Research, Munich, Germany;Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, United States;

关键词: pediatric HIV infection;    broadly neutralizing antibodies (bnAb);    T-follicular helper cells (Tfh);    T-follicular regulatory helper cells (Tfreg);    follicular CD8 T-cells;    germinal center;   

DOI  :  10.3389/fimmu.2018.01975

来源: DOAJ

【 摘 要 】

Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.

【 授权许可】

Unknown