CD4+CD25+ T regulatory (Treg) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of Treg cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25− T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring Treg cells, including expression of Foxp3, a crucial transcription factor of Treg cells, production of low levels of IL-2, high levels of IL-10 and TGF-β, and the ability to suppress CD4+CD25− T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-β in converting CD4+CD25− T cells into Treg cells because a neutralizing Ab against TGF-β, 1D11, completely abrogated the induction of Treg cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25− T cells to Treg cells because they produce low levels of TGF-β in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-β. Treatment of 1D11 also reduced the conversion of CD4+ T cells into Treg cells and subsequent Treg cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25− T cells to Treg cells through production of high levels of TGF-β, suggesting a possible mechanism through which tumor cells evade the immune system.

Of the couples unable to conceive without any identifiable cause, 30% are defined as having unexplained infertility. Management depends on duration of infertility and age of female partner. This review describes and comments on the definition and evidence for the management of unexplained infertility. A literature search was conducted in EMBASE, Medline, Ovid and Cochrane Database of Systematic reviews using the terms 'infertility', 'unexplained infertility', 'idiopathic infertility', 'definition of infertility', 'treatment options', 'intrauterine insemination', 'ovulation induction', 'Fallopian tube sperm', 'GIFT' and 'IVF'. There is no uniform definition for unexplained infertility. This varies in the literature depending on the duration of infertility and the age of the female partner. The treatment of unexplained infertility is empirical and many different regimens have been used. Among these are expectant management, ovulation stimulation with clomiphene citrate, gonadotrophins and aromatase inhibitors, Fallopian tube sperm perfusion, tubal flushing, intrauterine insemination, gamete intra-Fallopian transfer and IVF. The standard protocol is to progress from low-technology to high-technology treatment options. On the best available evidence, an algorithm for management is suggested. There is a definite need for multicentre randomized controlled trials to identify the best treatment option in unexplained infertility using a standard definition.

None.

BACKGROUND The present review summarizes the cellular action of TGF‐β in benign and malignant growth of the prostate. METHODS. TGF‐β is a pleiotropic growth factor. It plays an important role in the regulation of growth and differentiation in many cells. In benign prostatic epithelia, its action is mediated through a paracrine mechanism. It inhibits proliferation and induces apoptosis in prostatic epithelia. It provides a mechanism to maintain epithelial homeostasis in the prostate. In prostatic stroma, its continual action leads to smooth muscle differentiation. This effect of TGF‐β may regulate the development of prostatic smooth muscle nodules in benign prostatic hyperplasia. RESULTS As prostatic epithelial cells undergo malignant transformation, two major events occur regarding TGF‐β action. These include the loss of expression of functional TGF‐β receptors and overproduction of TGF‐β in malignant cells. The loss of expression of functional TGF‐β receptors provides a growth advantage to cancer cells over their benign counterparts. The overproduction of TGF‐β by cancer cells has a multitude of adverse consequences. TGF‐β can promote extracellular matrix production, induce angiogenesis, and inhibit host immune function. The biological consequence of these activities is an enhanced tumorigenicity in prostate cancer. Results of our recent studies with a rat prostate cancer model suggest that the immunosuppressive effect of TGF‐β seems to be the primary cause of tumor progression. This is because, if these cancer cells were engineered to reduce the production of TGF‐β, tumor growth was inhibited in syngeneic hosts but not in immune compromised hosts. CONCLUSIONS Our future research should take advantage of this knowledge to devise therapeutic strategies aimed at eradicating prostate cancer. Prostate 39:285–290, 1999. © 1999 Wiley‐Liss, Inc.

There are significantly improved outcomes when women are exposed to seminal plasma around the time of ovum pick-up or embryo transfer, with statistical significance for clinical pregnancy but not for ongoing pregnancy/live birth rates being achieved. This meta-analysis is limited by the small number of studies of variable methodology. Further research is required to determine the effect on live birth rate; however, this meta-analysis indicates a significantly improved clinical pregnancy rate and a potential method for improving IVF outcomes.

No abstract

TGF-β regulation of immune homeostasis has been investigated in the context of cytokine knockout (TGF-β null) mice, in which particular TGF-β isoforms are disrupted throughout the entire organism, as well as in B and T cell-specific transgenic models, but to date the immunoregulatory effects of TGF-β have not been addressed in the context of an in vivo mouse model in which multi-isoform TGF-β signaling is abrogated in multiple leukocyte lineages while leaving nonhemopoietic tissue unaffected. Here we report the development of a murine model of TGF-β insensitivity limited to the hemopoietic tissue of adult wild-type C57BL/6 mice based on retroviral-mediated gene transfer of a dominant negative TGF-β type II receptor targeting murine bone marrow. Unlike the lymphoproliferative syndrome observed in TGF-β1-deficient mice, the disruption of TGF-β signaling in bone marrow-derived cells leads to dramatic expansion of myeloid cells, primarily monocytes/macrophages, and is associated with cachexia and mortality in lethally irradiated mice reconstituted with dominant negative receptor-transduced bone marrow. Surprisingly, there was a notable absence of T cell expansion in affected animals despite the observed differentiation of most cells in the T cell compartment to a memory phenotype. These results indicate not only that TGF-β acts as a negative regulator of immune function, but that lack of functional TGF-β signaling in the myeloid compartment of adult mice may trigger suppression of lymphocytes, which would otherwise proliferate when rendered insensitive to TGF-β.

ISRCTN43430382.