*Purpose: T follicular helper (Tfh) cells are a subset of CD4⁺ T cells that specializes 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 Tfh cells 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 the depletion effect of mATG on Tfh, mice were immunized with NP-Ova (100 mcg/mouse, s.c.) and CFA on day 0, and received mATG (500 mcg/mouse, i.p.) on day 0 and day 4. Draining lymph nodes (dLNs) and blood were harvested and Tfh population (CD4⁺CXCR5⁺PD-1⁺) was examined on day 7.

*Results: While mATG was effective in depleting peripheral T cells (more than 90%) (Fig1A), cTfh (Fig1B) and rTfh in LN (Fig1C) were relatively spared. Furthermore, Tfh were still able to differentiate and help the GC reaction and class switching to IgG.

*Conclusions: mATG is effective in depleting T cells both in peripheral blood and secondary lymphoid organs. However, Tfh are resistant to its effect. The mechanisms of that remain uncertain and require further investigation. Since antibody-mediated rejection 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.

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