Role of interleukin 1 in the activation of T lymphocytes.

Abstract

The activation of T lymphocytes requires their stimulation via clonotypic antigen receptors as well as nonantigen-specific costimulators, the best defined of which is the cytokine interleukin 1 (IL-1). Recent studies have shown that murine CD4+ helper T lymphocytes consist of two nonoverlapping subsets that selectively utilize interleukin 2 (IL-2) or interleukin 4 as their autocrine growth factors and are called Thl and Th2 cells, respectively. We now show that ILfunctions as a costimulator for the proliferation of Th2 but not ofThl clones and only Th2 cells express high-affinity receptors for IL-1. Secretion of autocrine growth-promoting lymphokines by Thl and Th2 cells occurs after stimulation via the antigen receptor-CD3 complex and is neither dependent on nor affected by IL-1. These findings suggest that the activation of T lymphocytes can be divided into two stages, lymphokine secretion and proliferation, and only proliferation requires costimulators such as IL-1. Moreover, the prevailing view that IL-1 functions as a costimulator by inducing secretion of IL-2 or expression ofIL-2 receptors may not be generally applicable, because IL-2-producing Thl clones do not express receptors for IL-1 and are insensitive to this cytokine.

Interleukin 1 plays a major role in the development of Th2‐mediated immunity

“…Some reports suggest that IL-1 promotes proliferation of Th2 cells in vitro [14][15][16][17], while others suggest that in the absence of IL-1 signaling, exaggerated Th2 responses occur [18]; again others report no differences [19]. We have found that the absence of either IL-1a or IL-1b results in incomplete Th2 polarization both in vivo and in vitro.…”

“…Previous work suggests that IL-1a acts as a proliferation stimulus for Th cells [15,16,21,22]. To investigate if the decreased Th2 cytokine production in T. muris-infected IL-1a and IL-1b KO mice was related to reduced proliferation, we measured antigen-and mitogen-induced proliferation by [ 3 H]thymidine incorporation.…”

“…It has been demonstrated that IL-1 promotes T cell proliferation in response to antigens and lectins, inducing the expression of IL-2 and IL-2 receptor [12,13] and promoting the proliferation of some Th2 cell clones in vitro [14][15][16][17]. In contrast, other reports have suggested that exaggerated Th2-type responses develop in IL-1 receptor-deficient mice [18], while others report no effect on Th2-type responses [19].…”

T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region

“…[10][11][12][13][14] Cytokines in the IL-1 system (IL-1␣, IL-1␤ and IL-1 receptor antagonist (IL-1Ra)) are produced at the maternal-fetal interface during early pregnancy. 15 The IL-1 system may be involved in the regulation of Th1/Th2 cytokine production, since IL-1 can function as a costimulator for Th2 cell generation in both rodents and humans [16][17][18][19] and may influence IFN-␥ production mediated by natural killer (NK) and T cells. 20,21 Moreover, IL-1 has been implicated in implantation, 22 and trophoblast growth and invasion.…”

“…24 Altered IL-1 production may affect the balance of Th1/Th2 cytokine responsiveness, involving either pregnancy success or failure by two potential mechanisms. First, since IL-1␣ and IL-1␤ are important co-stimulators for Th2 cell proliferation, [16][17][18][19] decidual IL-1 may influence Th2 cell generation. Conversely, low IL-1␤ production at the maternal-fetal interface may reduce Th2-type cytokine production, and thus, in concert with elevated decidual IL-12 levels, favor a Th1-type response to the developing conceptus, which could contribute to early pregnancy failure.…”