A Novel Role of CD30L/CD30 Signaling by T-T Cell Interaction in Th1 Response against Mycobacterial Infection

Abstract

A CD30 ligand (CD30L, CD153) is a type II membrane-associated glycoprotein belonging to the TNF family. To illustrate the potential role of CD30L in CD4+ Th1 cell responses, we investigated the fate of Ag-specific CD4+ T cells in CD30L-deficient (CD30L−/−) mice after Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. The number of bacteria was significantly higher in organs of CD30L−/− mice than in wild-type (WT) mice 4 wk postinfection. The numbers of purified protein derivative- or Ag85B-specific-IFN-γ-producing-CD4+ T cells in spleen, lung, or peritoneal exudate cells were significantly fewer in CD30L−/− mice than in WT mice. During the infection, CD30L was expressed mainly by CD44+CD3+CD4+ T cells but not by CD3+CD8+ T cells, B cells, dendritic cells, or macrophages. Costimulation with agonistic anti-CD30 mAb or coculturing with CD30L-transfected P815 cells restored IFN-γ production by CD4+ T cells from BCG-infected CD30L−/− mice. Coculturing with CD30L+/+CD4+ T cells from BCG-infected WT mice also restored the number of IFN-γ+CD30L−/−CD4+ T cells. When transferred into the CD30L+/+ mice, Ag-specific donor CD30L−/− CD4+ T cells capable of producing IFN-γ were restored to the compared level seen in CD30L+/+ CD4+ T cells on day 10 after BCG infection. When naive CD30L+/+ T cells were transferred into CD30L−/− mice, IFN-γ-producing-CD4+ Th1 cells of donor origin were normally generated following BCG infection, and IFN-γ-producing-CD30L−/−CD4+ Th1 cells of host origin were partly restored. These results suggest that CD30L/CD30 signaling executed by CD30+ T-CD30L+ T cell interaction partly play a critical role in augmentation of Th1 response capable of producing IFN-γ against BCG infection.

CD30 Ligand Is a Target for a Novel Biological Therapy against Colitis Associated with Th17 Responses

“…Consistent with a previous report (36), a few but significant number of CD4 + T cells of spleen, MLN, and LPLs expressed CD30L in naive mice. CD30L expression on CD4 + T cells, especially in LPLs, was significantly increased on day 5 in DSS-induced acute colitis and on day 25 in DSS-induced chronic colitis (Fig.…”

“…The level of Th1-type cytokine IFN-g in T-LPLs was significantly lower in OXA-or TNBS-treated CD30L 2/2 mice than that in WT mice (29). We also found that CD30L 2/2 mice were susceptible to infection with bacillus Calmette-Guérin in association with reduced Th1 responses (36). These results suggested that CD30L/CD30 signaling is linked to Th1 cell responses and Th1-associated diseases.…”

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study

“…These results were interesting because, at cell line levels, elevated CD30 expression is considered to be one of the causes of constitutive NF-kappa B activation in ATL cells, thereby resulting in ATL development (Higuchi et al, 2005). Tang et al reported that CD30-CD30L signaling are important for T-cell regulation (Tang et al, 2008). Based on these results, in the microenvironment, it is conceivable that ATL stem cells produce sIL-2R and sCD30 to prevent activating T cell death by excess IL-2R signaling and cell death caused by CD30-CD30L interaction (Pornkuna et al, 2014b).…”

CD30 Is Required for Activation of a Unique Subset of Interleukin-17A-Producing γδ T Cells in Innate Immunity against Mycobacterium bovis Bacillus Calmette-Guérin Infection

“…However, a number of recent studies indicated that CD30L/CD30 signaling is also linked to Th1 or regulatory T cell responses and their associated diseases (30)(31)(32)(33)(34)(35). We have recently found that CD30L/CD30 signaling executed by T cell-T cell interaction plays a novel role in Th1 and Th17 cell differentiation in vitro and in vivo (36)(37)(38). In this regard, CD30L/CD30 signaling may be dispensable for differentiation of a specific Th cell subset in a physiological pathway, while it may be required for the activation and/or amplification of T cells irrespective of the T cell subset in the periphery.…”

“…Recently, we and others reported that CD30L and CD30 play an important role in acquired immunity against mycobacterial infection by amplifying the Th1 response (32,36). However, the potential role of CD30L/CD30 signaling in controlling host defense through activation of IL-17A-producing T cells against mycobacterial infection is unknown.…”