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T cell depletion increases humoral response by favoring T follicular helper cells expansion.
- Source :
-
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Jul; Vol. 22 (7), pp. 1766-1778. Date of Electronic Publication: 2022 Apr 15. - Publication Year :
- 2022
-
Abstract
- Antibody-mediated rejection is a major cause of long-term graft loss in kidney transplant patients. T follicular helper (Tfh) cells are crucial for assisting B cell differentiation and are required for an efficient antibody response. Anti-thymocyte globulin (ATG) is a widely used lymphocyte-depleting induction therapy. However, less is known about how ATG affects Tfh cell development and donor-specific antibody (DSA) formation. We observed an increase in circulating Tfh cells at 6 months after kidney transplant in patients who received ATG. Using an NP-OVA immunization model, we found that ATG-treated mice had a higher percentage of Tfh cells, germinal center B cells, and higher titers of antigen-specific antibodies compared to controls. ATG-treated animals had lower levels of IL-2, a known Bcl-6 repressor, but higher levels of IL-21, pSTAT3 and Bcl-6, favoring Tfh differentiation. In a mouse kidney transplant model, ATG-treated recipients showed an increase in Tfh cells, DSA and C4d staining in the allograft. Although ATG was effective in depleting T cells, it favored the expansion of Tfh cells following depletion. Concomitant use of IL-2, tacrolimus, or rapamycin with ATG was essential to control Tfh cell expansion. In summary, ATG depletion favors Tfh expansion, enhancing antibody-mediated response.<br /> (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Details
- Language :
- English
- ISSN :
- 1600-6143
- Volume :
- 22
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Publication Type :
- Academic Journal
- Accession number :
- 35320600
- Full Text :
- https://doi.org/10.1111/ajt.17038