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Bacterial Vaginosis and T-Cell Dysfunction

1:14:43 recording · AUTO · 2 speakers

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Brief overview

Two immunologists review evidence that bacterial vaginosis exhausts cervical T cells and that somatic hypermutation births new specificities.

  1. The healthy vagina wants a monoculture, not diversityLactobacillus crispatus dominance keeps the pH low; polymicrobial state types bring inflammation and BV.
  2. BV leaves cervical T cells exhausted, not absentCD39 and CD101 up, TCF1 stem-like cells down, granzyme B reduced, with more CCR5 for HIV entry.
  3. Hypermutation can birth specificities the repertoire never hadHA-only B cells gained nanomolar binding to ova, PCC and CGG they could not bind before.
Executive Summary AI
  • Steph Langel presents "Bacterial Vaginosis Associates with Dysfunctional T-Cells and Altered Soluble Immune Factors in the Cervical Vaginal Tract", first-authored by Finn McLean, with Jennifer Lund and Jaram Lingapa contributing equally as senior authors from Fred Hutch, the University of Washington and Nairobi.2:41
  • The Kinga cohort covered 204 Kenyan women, sampled by vaginal swab, ectocervical biopsy, PBMCs, cervical vaginal fluid and serum, and read out by flow cytometry, immunofluorescent imaging and Luminex cytokine profiling.8:50
  • Women with BV showed higher CCR5 and HLA frequencies, raised CD39 and CD101 markers of exhaustion, fewer TCF1-positive stem-like CD4 cells and CD8 cells with reduced granzyme B, a locally suppressed state in a condition that hits about one in four women and recurs in one in two after antibiotics.12:12
  • Cindy Leifer then takes "Somatic hypermutation generates antibody specificities beyond the primary repertoire", first author Tang Zhu and last author Dwayne Westman at Harvard, published in Immunity over the summer, which challenges the textbook idea that hypermutation only refines an existing specificity.20:46
  • Using RAG-knockout mice whose B cells carry only an HA-specific receptor, repeated immunisation with ovalbumin, PCC or CGG drove those bystander cells into germinal centres with up to 20, 25 mutations and yielded cloned antibodies binding ova in the nanomolar range.47:42
Key Quote
“So the local immune dysregulation, it's not just systemic in blood.”
— Steph Langel14:38
Key Quote
“I mean, they're just undergoing Darwinian evolution all the time in our body.”
— Cindy Leifer20:30
Key Quote
“So really you can birth these new antibodies from an existing antibody that has completely different specificity.”
— Cindy Leifer50:40