The normal prostate, like all other organs, contains endogenous inflammatory cells consisting of scattered stromal and intraepithelial T and B lymphocytes81,82
, macro phages and mast cells. However, most adult prostate tissues contain increased inflammatory infiltrates, albeit the extent and type of inflammation are variable (for a review, see REF. 83
). In terms of the biology of the inflammatory cells and the nature of the immune response in the prostate, most of the work has focused on BPH tissues in comparison with samples from the normal transition zone, and sometimes with carcinoma samples that have occurred in this region. Steiner et al.
have examined the immunophenotypic and biological properties of chronic inflammatory cells in BPH and normal prostate tissues84–86
. They have shown that of the increased CD45+
cells (all leukocytes express CD45 and non-leukocytes do not), 70–80% of these are CD3+
T lymphocytes, whereas 10–15% are CD19+
B lymphocytes. Macrophage numbers were also increased in these inflammatory lesions. In terms of the phenotype of the T cells, there is a reversed CD8:CD4 ratio, such that most T cells present in the normal areas expressed CD8, but most T cells in the inflamed areas expressed CD4. In terms of T-cell receptors (TCRs), 90% of the cells represent ‘standard’ αβ T cells (which express TCRαβ), with less than 1% representing γδ T cells. Class II major histocompatability antigen (HLADR), which indicates whether T cells are ‘activated’ by antigen signalling, is present on approximately 40% of the CD3+
T cells, and many of these T cells expressed CD45RO, indicating that these are ‘antigen experienced’ T cells85
. None of the T cells in the normal prostate epithelium showed evidence of either activation or of being antigen experienced T cells.
T cell responses can be divided into several different types that are classified according to their cytokine profile. TH
1 cells produce interferon-γ and TNFα, whereas TH
2 cells produce interleukin 4 (IL4), IL5 and IL13. Regulatory T (TReg
) cells, which can suppress adaptive T-cell responses and autoimmunity, are characterized by the expression of CD25 and the transcription factor FOXP3, and they secrete transforming growth factor-β (TGFβ). In BPH, Marberger’s group determined that the T-cell response is complex, in that although TH
0 (T cells that do not express any of the indicated cytokines) and TH
1 cells were predominant in the inflammatory lesions of BPH and in carcinoma, some features of a TH
2 response were also present. Unfortunately, at this point similar experiments have not been performed in the other zones of the prostate, or in areas of focal atrophy or PIN of the peripheral zone. The need for further understanding in this area is crucial, as is illustrated by the findings that microbially-driven inflammation can lead to colon cancer in mice, and that the prior transfer of TReg
cells that express CD4 and CD25 prevents the inflammatory response that leads to colon cancer in these animals87
. Recently Miller et al.88
, have shown that CD4+
T cells, with properties of TReg
cells including the expression of the FOXP3 protein, are present in increased numbers in clinically localized prostate cancer tissues, compared with normal prostate tissues. Exciting new data from several groups suggest the importance of a new subset of CD4-effector T cells known as TH
17 cells, which develop through distinct cytokine signals (especially IL23) with respect to those involved in TH
1 and TH
2 responses, and are characterized by the production of IL17 (REF. 89
). These cells are required for inflammation in arthritis and encephalitis models89
, and IL23 is required for skin cancer formation in response to carcinogen exposure in mice90
. A potential role for TH
17 cells in prostatic inflammation had already been demonstrated by Steiner et al.
before the TH
17 cell lineage had been recognized as being as distinct. They showed that activated T cells in BPH tissue and in prostate cancer express high levels of IL17 (REF. 85
). Further work to more fully elucidate the phenotypic and biological properties of all T-cell subsets in the prostate is required before we can understand the significance of acquired cell-mediated immunity in prostate carcinogenesis. Methods such as the quantitative image analysis of immunohistochemically stained inflammatory cell subsets, as well as flow cytometry for these subsets using tissues isolated from histologically defined areas, will be crucial to obtain such data.