Year: 2019
Type: article
Abstract: INTRODUCTION: T follicular helper (Tfh) cells are a subset of CD4+ T cells that specialize in providing help for germinal center (GC) reactions where B cells are activated, differentiate and produce high-affinity antibodies.In addition to those residing in lymph nodes (rTfh), a small percentage of Tfhcells called circulating Tfh (cTfh) can be found in peripheral blood. In the setting of kidney transplantation (KT), higher percentages of cTfh have been associated with donor-specific-antibodies and chronic antibody mediated rejection. Anti-thymocyte globulin (ATG) is a widely used potent depleting induction therapy, however, little is known about its effect on Tfh population. We aimed to analyze the effect of mouse ATG (mATG) on both secondary lymphoid-resident and circulating Tfh. METHODS: We generated mATG by immunizing rabbits with splenocytes retrieved from three different mouse strains (DBA/B, C3H and SJL) followed by purification with ammonium sulfate precipitation. To examine if mATG could deplete “formed” Tfh, mice were immunized with NP-Ova (100 mcg/mouse, s.c.) and CFA on day 0 (GC formation, Fig1A), and received mATG (500 mcg/mouse, i.p.) on day 7. Draining lymph nodes (dLNs) and blood were harvested and Tfh population (CD4+CXCR5+PD-1+) was examined on day 9. While mATG was effective in depleting circulating and resident non-Tfh cells >90% (Fig1B-1C), cTfh (Fig1B) and rTfh in LN (Fig1C) were relatively spared. Furthermore, when mATG was given on day 0 and 4 after immunization, Tfh were still able to differentiate and help the GC reaction (Fig 1D). RESULTS: CONCLUSIONS: mATG is effective in depleting T cells both in peripheral blood and SLOs. However, Tfh seem to show resistance to its effect. The mechanisms involved remain uncertain and require further investigation. Since ABMR is a dominant cause of graft failure, investigating the mechanism of this resistance is crucial for the development of more effective therapies in restraining Tfh cells to prevent the production of donor-specific antibodies.
Institutions: Hospital Del Mar, Brigham and Women's Hospital
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2952776887