Inhibitory effect of interleukin‐16 on interleukin‐2 production by CD4⁺ T cells

Abstract

SUMMARYSignalling through CD4 by human immunodeficiency virus (HIV )-1 envelope glycoprotein (gpl20) and/or anti-CD4 antibodies can promote T-cell activation and anergy. Interleukin (IL)-16 is a competence growth factor for CD4+ T cells that can induce a G 0 to G 1 cell cycle transition but cannot induce cell division. The receptor of this cytokine is thought to be the CD4 molecule, although the binding epitope of IL-16 differs from that of HIV. We have demonstrated that both HIV-1/gp120 and IL-16 induced CD4+ T-cell dysfunction, as indicated by suppression of mitogeninduced IL-2 production. Two anti-CD4 antibodies with different binding sites on CD4 also showed an inhibitory effect on IL-2 production. These results indicate that promotion of CD4+ T-cell anergy via the CD4 molecule does not depend on the binding sites of the CD4 ligands.

The HIV protease inhibitor Indinavir inhibits cell-cycle progression in vitro in lymphocytes of HIV-infected and uninfected individuals

“…35,36 IL-16 is known to inhibit anti-CD3-induced lymphocyte activation and lymphoproliferation. 39,40 These observations, together with our findings, suggest that IDV may be blocking cell-cycle progression in lymphocytes, possibly by enhancing the levels of IL-16 production in association with the blocking of proteasomal activity.…”

“…37,38 Additionally, PIs have been reported to influence cytokines that regulate lymphocyte proliferation. [33][34][35][36]39,40 It has been shown that the serum levels of interleukin 16 (IL-16) are increased in patients on IDV-containing drug regimens. 35,36 IL-16 is known to inhibit anti-CD3-induced lymphocyte activation and lymphoproliferation.…”

Preferential Migration of T Regulatory Cells Induced by IL-16

“…This suggests that the IL-16 effect on Foxp3 expression is independent of IL-2. This concept is further supported by the findings that IL-16 stimulation inhibits IL-2 production by activated T cells (36). In addition, studies have now identified the role of IL-2 for Foxp3 expression as primarily for maintaining the homeostatic state of natural CD4 ϩ CD25 ϩ Treg cells; however, it is not required for the induction phase (37,38).…”

Synovial Fibroblasts from Patients with Rheumatoid Arthritis, Like Fibroblasts from Graves’ Disease, Express High Levels of IL-16 When Treated with Igs against Insulin-Like Growth Factor-1 Receptor

“…For instance, IL-16 induces cell cycle progression from G 0 to G 1 and enhances the display of the IL-2R (31). It renders pre-exposed T cells refractory to antigenic stimulation, promoting, as a consequence, anergy and enhanced Fas expression (32). IL-16 causes cross-desensitization of CCR5 and CXCR4 (33,34).…”