Despite the broad rehabilitative potential of aquatic exercises, the relationship between aquatic exercise and the immune system has not been fully elucidated to date. In particular, there are few specific and delicate immunological approaches to the effect of water temperature on immunity. Thus, we examined the effect of water temperature on immunity during aquatic exercise. The animal tumor model was adopted to examine the impact of aquatic exercise at thermoneutral temperature (TT; 29°C) on immunity compared with aquatic exercise at body temperature (BT; 36°C). Tumor-bearing mice were made to swim in TT water or in BT water for 3 wk and immune cells and their functional activity were analyzed using FACS. Tumor growth was significantly suppressed in mice that exercised in TT than in BT water. The tumor control correlated with the increased number of NK (2-fold), γδT cells (2.5-fold), NKT (2.5-fold), and cytotoxic CD8 + T cells (1.6-fold), which play a critical role in anti-tumor immune responses. Furthermore, the functional activity was dramatically improved in the TT group, showing enhanced production of IFNγ in CD8 + T cells compared with the BT group. This study demonstrates that aquatic exercise in TT water may improve protective immune responses more effectively than in BT water. Although the effects of water temperature on immune function need further verification in humans, this study suggests that water temperature in human hydrotherapy may be important for improving immune function.

Previous studies have shown that soluble common γ-chain (sγc) modulates CD4 T cell immunity with antagonistic functions in γc cytokine signaling. However, the role of sγc in functional properties of effector CD8 T cells has not been fully defined. In this study, we report a new mechanism by which the anti-tumor activity of mouse CD8 T cells is suppressed in sγc of their own producing. While sγc significantly inhibits cytotoxicity of CD8 T cells, blocking sγc production by genetic modification leads to potentiated effector function of CD8 T cells, establishing persistent CD8 T cells. This is due to the modulation of IL-2 and IL-15 signaling, which is required for expansion and survival of CD8 T cells as well as for optimal cytotoxic activity. More efficient management of tumor growth was achieved by an adoptive transfer of sγc-deficient CD8 T cells than that of wild-type or sγc-overexpressing CD8 T cells. Blocking of IL-2 and IL-15 signaling by sγc attenuates the capacity of CD8 T cells to mount an optimal response to the tumor, with both quantitative and qualitative effects on antigen-specific CD8 T cells. These results could have a critical implication for the generation and survival of optimal effector T cells for adoptive immunotherapy of cancer.

IL-17 produced by Th17 cells has been implicated in the pathogenesis of rheumatoid arthritis (RA). It is important to prevent the differentiation of Th17 cells in RA. Homodimeric soluble γc (sγc) impairs IL-2 signaling and enhances Th17 differentiation. Thus, we aimed to block the functions of sγc by inhibiting the formation of homodimeric sγc. The homodimeric form of sγc was strikingly disturbed by sγc-binding DNA aptamer. Moreover, the aptamer effectively inhibited Th17 cell differentiation and restored IL-2 and IL-15 signaling impaired by sγc with evidences of increased survival of T cells. sγc was highly expressed in SF of RA patients and increased in established CIA mice. The therapeutic effect of PEG-aptamer was tested in CIA model and its treatment alleviated arthritis pathogenesis with impaired differentiation of pathogenic Th17, NKT1, and NKT17 cells in inflamed joint. Homodimeric sγc has pathogenic roles to exacerbate RA progression with differentiation of local Th17, NKT1, and NKT17 cells. Therefore, sγc is suggested as target of a therapeutic strategy for RA.

Cigarette smoking (CS) is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc) has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE) mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN) is systemically reduced in the CSE group. Overexpression of sγc enhances the cellularity and IFNγ production of CD8 T cells in LN and also enhances Th1 and Th17 differentiation of CD4 T cells in the respiratory tract. Mechanistically, the downregulation of sγc expression mediated by CSE is required to prevent excessive inflammatory T cell responses. Therefore, our data suggest that sγc may be one of the target molecules for the control of immunopathogenic progresses in COPD.

The common gamma chain (γc) is the central signaling unit for a number of cytokine receptors collectively known as the γc cytokine receptor family. γc is critical for ligand binding and signaling by γc cytokines. γc cytokine signaling had been thought to be mainly regulated by cytokine-specific receptor α chain expression levels with little or no effect by γc surface levels because γc expression was presumed to remain unchanged during T-cell activation and development. The extent of γc cytokine responses is thought to be regulated by cytokine specific receptor subunits and not by the γc receptor. In contrast to this prevailing view, we have recently reported that γc itself actively regulates γc cytokine responses. Interestingly, γc exerted its regulatory effects not only as a conventional membrane receptor protein but also as a secreted protein whose expression was upregulated upon T-cell stimulation. Here we will review how a soluble form of γc, which is generated by alternative splicing, regulates γc cytokine signaling and plays a role in controlling immune activation related to autoimmune disease.