IL-7 and IL-15 combined with strong TCR stimulation decrease Treg
suppressive activity in healthy donors and patients with rheumatoid
arthritis
Abstract
Homeostatic proliferation (HP) is a physiological process to
reconstitute the T-cell pool after lymphopenia with IL-7 and IL-15 being
the key cytokines regulating the process. However, there is no evidence
whether these cytokines influence the function of regulatory T cells
(Tregs). Since lymphopenia often accompanies autoimmune diseases, we
decided to study the proliferation rate and function of Tregs stimulated
by IL-7 and IL-15 in patients with rheumatoid arthritis (RA) compared to
healthy donors (HD). The study used peripheral blood from 14 RA patients
and 18 HD. Proliferation of purified
CD3+CD4+CD25+CD127lo
cells was assessed by flow cytometry using CFSE. Tregs were stimulated
by anti-CD3, IL-7, IL-15, IL-7, or IL-15 combined with anti-CD3, and by
IL-2+anti-CD3, and their functional activity was evaluated in each case
by CD4+ and CD8+ cells proliferation
inhibition. The suppressive activity of peripheral Tregs did not differ
between RA and HD; however, it significantly decreased when IL-7 or
IL-15 were applied together with strong TCR stimulation with anti-CD3
antibodies. Herewith Treg proliferation caused by IL-7 and IL-15 was
lower in RA than in HD. The revealed decrease in Treg suppressive
activity can lead to the proliferation of potentially self-reactive
T-cell clones, which can receive relatively strong TCR signals. This may
be another explanation of why lymphopenia is associated with the
development of autoimmune diseases. The revealed decrease of Treg
proliferation under IL-7 and IL-15 may lead to a delay in Treg pool
reconstitution in patients with rheumatoid arthritis.