Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

Abstract

Effective antibody responses are essential to generate protective humoral immunity. Different inflammatory signals polarize T cells towards appropriate effector phenotypes during an infection or immunization. Th1 and Th2 cells have been associated with the polarization of humoral responses. However, T follicular helper cells (Tfh) have a unique ability to access the B cell follicle and support the germinal center (GC) responses by providing B cell help. We investigated the specialization of Tfh cells induced under type-1 and type-2 conditions. We first studied homogenous Tfh cell populations generated by adoptively transferred TCR-transgenic T cells in mice immunized with type-1 and type-2 adjuvants. Using a machine learning approach, we established a gene expression signature that discriminates Tfh cells polarized towards type-1 and type-2 response, defined as Tfh1 and Tfh2 cells. The distinct signatures of Tfh1 and Tfh2 cells were validated against datasets of Tfh cells induced following lymphocytic choriomeningitis virus (LCMV) or helminth infection. We generated single-cell and spatial transcriptomics datasets to dissect the heterogeneity of Tfh cells and their localization under the two immunizing conditions. Besides a distinct specialization of GC Tfh cells under the two immunizations and in different regions of the lymph nodes, we found a population of Gzmk+ Tfh cells specific for type-1 conditions. In human individuals, we could equally identify CMV-specific Tfh cells that expressed Gzmk. Our results show that Tfh cells acquire a specialized function under distinct types of immune responses and with particular properties within the B cell follicle and the GC.

People
Kumar, Saumya
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Basto, Afonso P.
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Ribeiro, Filipa
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Almeida, Silvia C.P.
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Campos, Patricia
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Peres, Carina
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Pulvirenti, Nadia
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Al-Khalidi, Sarwah
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Kilbey, Anna
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Tosello, Jimena
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Piaggio, Eliane
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Russo, Momtchilo
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Gama-Carvalho, Margarida
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Coffelt, Seth B.
Author

Churchhouse, Antonia M.D. and Billard, Caroline V. and Suzuki, Toshiyasu and Pohl, Sebastian O.G. and Donnelly, Kevin and Nixon, Colin and Arends, Mark J. and Din, Shahida and Kirkwood, Kathryn and Marques Junior, Jair and Von Kriegsheim, Alexander and Coffelt, Seth B. and Myant, Kevin B. (2024) Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression. Oncogene, 43 (42). pp. 3094-3107. ISSN 0950-9232

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

Dawson, Amy and Zarou, Martha M. and Prasad, Bodhayan and Bittencourt-Silvestre, Joana and Zerbst, Désirée and Himonas, Ekaterini and Hsieh, Ya-Ching and van Loon, Isabel and Rodriguez Blanco, Giovanny and Ianniciello, Angela and Kerekes, Zsombor and Krishnan, Vaidehi and Agarwal, Puneet and Almasoudi, Hassan and McCluskey, Laura and Hopcroft, Lisa E.M. and Scott, Mary T. and Baquero, Pablo and Dunn, Karen and Vetrie, David and Copland, Mhairi and Bhatia, Ravi and Coffelt, Seth B. and Tiong, Ong Sin and Wheadon, Helen and Zanivan, Sara and Kirschner, Kristina and Helgason, G. Vignir (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15: 1090. ISSN 2041-1723

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Roberts, Ed
Author

Hargrave, Kerrie E. and Worrell, Julie C. and Pirillo, Chiara and Brennan, Euan and Masdefiol Garriga, Andreu and Gray, Joshua I. and Purnell, Thomas and Roberts, Edward W. and MacLeod, Megan K.L. (2024) Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells. Mucosal Immunology, 17 (5). pp. 843-857. ISSN 1933-0219

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

Bentley-Abbot, Calum and Heslop, Rhiannon and Pirillo, Chiara and Chandrasegaran, Praveena and McConnell, Gail and Roberts, Ed and Hutchinson, Edward and MacLeod, Annette (2024) An easy to use tool for the analysis of subcellular mRNA transcript colocalisation in smFISH data. Scientific Reports, 14: 8348. ISSN 2045-2322

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Geginat, Jens
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Florindo, Helena F.
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Graca, Luis
Author

Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis (2024) Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue. Cell Discovery, 10: 64. ISSN 2056-5968

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Information
Title:
Specialized Tfh cell subsets driving type-1 and type-21 humoral responses in lymphoid tissue
Creators:
Kumar, Saumya and Basto, Afonso P. and Ribeiro, Filipa and Almeida, Silvia C.P. and Campos, Patricia and Peres, Carina and Pulvirenti, Nadia and Al-Khalidi, Sarwah and Kilbey, Anna and Tosello, Jimena and Piaggio, Eliane and Russo, Momtchilo and Gama-Carvalho, Margarida and Coffelt, Seth B. and Roberts, Ed W. and Geginat, Jens and Florindo, Helena F. and Graca, Luis
Identification Number:
10.1038/s41421-024-00681-0
Date:
4 June 2024
Divisions:
College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Publisher:
Nature Publishing Group
Additional Information:
This work was supported by ENLIGHT-TEN project, European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 675395 to S.K.; UIDB/04046/2020 and UIDP/04046/2020 Centre grants (to BioISI) from the FCT, Portugal to M.G.-C.; Institut National de la Santé et de la Recherche Médicale, Labex DCBIOL (ANR-10-IDEX-0001-02 PSL and ANR-11-LABX0043), SIRIC INCa-DGOS-Inserm_12554 to E.P.; FAPESP/19906/ 2014 to M.R.; and HR22-00741 from Fundacion la Caixa, FAPESP/19906/2014, and 2022.04903.PTDC, from the FCT to L.G. A.P.B. was supported by PTDC/CVTCVT/31840/2017 from the FCT, Portugal.
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URI:
https://pub.demo35.eprints-hosting.org/id/eprint/239
Item Type:
Article
Depositing User:
Unnamed user with email ejo1f20@soton.ac.uk
Date Deposited:
11 Jun 2025 16:36
Revision:
25
Last Modified:
12 Jun 2025 11:15
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