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The allograft inflammatory factor-1 (AIF-1) is a 17 kDa interferon-gamma (IFN-gamma) inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA class III genomic region. Three proteins including ionized Ca(2+)-binding adaptor 1, microglia response factor-1, and daintain are identical with AIF-1. The expression of AIF-1 was mostly limited to the monocyte/macrophage lineage, and augmented by cytokines such as IFN-gamma. It was assumed that AIF-1 was a novel molecule involved in inflammatory responses, allograft rejection, as well as the activation and function of macrophages. However, it has been reported that AIF-1 is also expressed in macrophages and microglial cells in autoimmune diseases such as experimental autoimmune encephalomyelitis, neuritis and uveitis models, suggesting that AIF-1 may play a pivotal role in autoimmunity. In the present manuscript, the genomic and functional characteristics of AIF-1 family proteins as well as their immune regulatory effects are reviewed.

Antigen-presenting cells (APCs) play a crucial role in both innate and adaptive immunity. The mechanisms for APCs to distinguish self and nonself have not been uncovered. In the present manuscript, we hypothesized the balance between the activating and inhibiting receptors on APCs will control the state of APCs. In general, they keep balanced by the endogenous ligands so that APCs are in a non-activating state in the naïve bodies. However, foreign antigens or altered self cells will trigger the activating/inhibiting receptors positively or negatively, so these receptor-mediated signals into APCs will be in tendency to be unbalanced. As long as the activating signals are over the inhibiting receptors, APCs will then be activated to function. This hypothesis will help us to explain how APCs can distinguish self and nonself antigens as well as their close relationships with the occurrence of autoimmune diseases. The activated state of APCs in the early stage of autoimmune diseases may be due to imbalance of the activating/inhibiting receptors on APCs triggered by host endogenous ligands. On the other hand, the poor immunity against tumor cells in the late stage of tumor patients may be partially due to the so-called "tolerance" state of APCs in hosts. We believe that, with the proving by the coming evidences, the impacts of the present hypothesis on basic and clinical immunology would be significant.

Biological effects of low-dose radiation (LDR) in somatic cells have captured the interest of radiobiologists for the last two decades. Apoptosis of germ cells is required for normal spermatogenesis and often occurs through highly conserved events, including the transfer of vital cellular materials to the growing gametes following death of neighboring cells. Apoptosis of germ cells also functions in diverse processes, including removal of abnormal or superfluous cells at specific checkpoints, establishment of caste differentiation, and individualization of gametes. Moreover, germ cells are very sensitive to radiation-induced genomic and cytological effects. Therefore, induction of germ-cell apoptosis has been observed in the testis of animals exposed to both high-dose radiation (HDR) and LDR. Exposure of male germ cells to LDR induces a stimulating effect, while exposure to HDR causes an inhibitory effect on the metabolism, antioxidant capacity, and proliferation and maturation of cells, a phenomenon termed hormesis. Preexposure to LDR also protects cells from subsequently HDR-induced genomic and cytological effects, a phenomenon termed adaptive response. This review describes the features of male germ-cell apoptosis. It reviews the evidence that LDR induces the hormesis and adaptive responses in the male germ cells in terms of apoptosis. This review also discusses the possible effects of LDR-induced apoptotic hormesis and adaptive response on the modulation of inheritable genomic damage caused by subsequent radiation exposure to male germ cells.

Macrophages isolated from various tissues manifest differences in cell shape, the expression of surface markers, as well as metabolic and functional activities. However, the heterogeneity of macrophages expressing the same marker in different tissues has not been fully addressed. In the present study, mouse F4/80+ peritoneal exudate macrophages (PEMs) and splenic macrophages (SPMs) appeared similar in most respects. But the percentages of cells expressing CD80, CD40, MHC-II, TLR2, or TLR4, but not CD11c, CD54, or CD23, in freshly isolated F4/80+ SPMs were significantly higher than those in PEMs, whereas the levels of CD86+ cells in F4/80+ SPMs were markedly lower than those in PEMs. After lipopolysaccharide (LPS) stimulation, F4/80+ SPMs expressed significantly higher levels of CD86, CD40, or MHC-II than F4/80+ PEMs, but not CD11c, CD80, CD54, or CD23. F4/80+ SPMs had remarkably lower non-opsonic phagocytotic capacity against chicken RBCs or allo-T cells than PEMs as determined by two-photon microscopes and flow cytometry. SPMs produced markedly more NO than PEMs when cultured with LPS or allo-T cells. Furthermore, SPMs exhibited stronger immunogenicity than PEMs, as determined by the ability to stimulate T cell proliferation, delayed type hypersensitivity, and IFN-gamma production. The data showed the differences between SPMs and PEMs with regard to the phenotypes, phagocytosis, and immunogenicity, which may offer important information for us to better understand the distinguished immune responses of macrophages in spleens and the peritoneal cavity., (Copyright 2006 Wiley-Liss, Inc.)

Innate immunity plays a role in fighting against invading microorganisms. Emerging evidence suggests that in addition to responding to pathogen-associated molecular patterns of microorganisms, Toll-like receptors (TLRs) can be activated by endogenous ligands expressed by mammalian cells. Clinical and laboratory studies have shown that TLRs may participate in organ graft rejection and transplant immune tolerance, which are briefly reviewed in the present manuscript.

Hormetic and adaptive responses induced by low-level radiation in hematopoietic and immune systems have been observed, as shown by stimulatory effects on cell growth and resistance to subsequent radiation-induced cytogenetic damage. However, in terms of cell death by apoptosis, the effects of low-level radiation are controversial: Some studies showed decreased apoptosis in response to low-level radiation while others showed increased apoptosis. This controversy may be related to the radiation doses or dose rates and also, more importantly, to the cell types. Testes are one of the most radiosensitive organs. The loss of male germ cells after exposure to ionizing radiation has been attributed to apoptosis. In the present study, the effects of low-level radiation at doses up to 200 mGy on mouse male germ cells in terms of apoptosis and the expression of apoptosis-related proteins were examined at different times after whole-body exposure of mice to low-level radiation. In addition, the effect of pre-exposure to low-level radiation on subsequent cell death induced by high doses of radiation was examined to explore the possibility of low-level radiation-induced adaptive response. The results showed that low-level radiation in the dose range of 25-200 mGy induced significant increases in apoptosis in both spermatogonia and spermatocytes, with the maximal effect at 75 mGy. The increased apoptosis is most likely associated with Trp53 protein expression. Furthermore, 75 mGy low-level radiation given pre-irradiation led to an adaptive response of seminiferous germ cells to subsequent high-level radiation-induced apoptosis. These results suggest that low-level radiation induces increased apoptosis in male germ cells but also induces a significant adaptive response that decreases cell death after a subsequent high-dose irradiation.