PT - JOURNAL ARTICLE AU - Igor Santiago-Carvalho AU - Gislane Almeida-Santos AU - Bruna Gois Macedo AU - Caio Cesar Barbosa-Bomfim AU - Fabricio Moreira Almeida AU - Marcos Vinícios Pinheiro Cione AU - Trupti Vardam-Kaur AU - Mia Masuda AU - Sarah Van Dijk AU - Bruno Marcel Melo AU - Rogério Silva do Nascimento AU - Rebeka da Conceição Souza AU - Alba Lucínia Peixoto-Rangel AU - Robson Coutinho-Silva AU - Mario H. Hirata AU - José Carlos Alves-Filho AU - José Maria Álvarez AU - Elena Lassounskaia AU - Henrique Borges da Silva AU - Maria Regina D’Império-Lima TI - T cell-specific P2RX7 favors lung parenchymal CD4<sup>+</sup> T cell accumulation in response to severe lung infections AID - 10.1101/2022.09.19.508603 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.09.19.508603 4099 - http://biorxiv.org/content/early/2022/09/19/2022.09.19.508603.short 4100 - http://biorxiv.org/content/early/2022/09/19/2022.09.19.508603.full AB - CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observed that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3 and favors in situ proliferation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.Competing Interest StatementH.BdS. is an advisor for International Genomics Consortium. The remaining authors do not have any competing interests.