Trends in Immunology
ReviewSpecial issue: novel functions of neutrophilsPolymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?
Introduction
“Misery acquaints a man with strange bedfellows” says The Tempest's stranded sailor, when he takes refuge from a storm with an alleged monster [1]. And indeed, polymorphonuclear neutrophils (PMN) and T lymphocytes seem to be strange bedfellows, because – according to immunology textbooks – they belong to different compartments of the immune system. Nevertheless, they do interact under certain pathophysiological conditions, as we will discuss below.
PMN are the main protagonists of the innate immune response, archaic cells, that more or less indiscriminately phagocytose particulate material and release cytotoxic and bactericidal entities. The short lifespan of the PMN and the rapid refurbishing of their peripheral cell pool by release of mature cells from the bone marrow reservoirs qualify PMN as the perfect single-use cell. By contrast, T lymphocytes are versatile cells that are activated in an antigen-specific manner to assume helper, effector, or regulatory functions, thus adapting to the immediate requirements. T cells determine the specificity of the ensuing immune response and of the developing immunologic memory.
PMN activation is invariably linked to the innate defence against bacterial infection, whereas T cell activation and functions are associated with virus infections, defence against tumours, the development and progression of chronic inflammatory processes, autoimmune phenomena and the tolerance towards the foetus in successful pregnancy. This oversimplification, however, no longer holds true: there is increasing evidence for T cell activation in response to bacterial infection and for the co-localization of PMN and T cells at sites of persistent infections, chronic inflammation or in tumours. Moreover, numerous means of communication between PMN and T cells have been identified, and there is ample evidence for mutual influence. Here, we discuss the interactions of PMN and T cells in bacterial infection and in chronic inflammatory disease, the link between PMN and the adaptive immune response and the impact of these interactions on the quality of the immune response in physiological and pathological conditions, using pregnancy and the defence against tumours as examples, respectively.
Section snippets
PMN and T cells in bacterial infection
Bacterial infections result in the activation of PMN. There is growing evidence, however, for the activation and expansion also of T cells. Although most data are derived from experimentally induced infections with intracellular bacteria in mice [2], T cell activation is also observed in patients with a variety of bacterial infections [3]. In patients with implant-associated osteomyelitis, a prototype of a localized, persistent bacterial biofilm infection, the majority of infiltrated cells were
PMN and T cells in autoimmune and chronic inflammatory diseases
A common denominator of autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis (RA), primary vasculitis, multiple sclerosis and inflammatory bowel disease, is a dysfunctional immune response, notably within the T cell compartment. The acute phases of these diseases, however, are also associated with PMN activation and their infiltration into the affected organs. In diseases such as RA or Wegener's granulomatosis, a primary vasculitis, the extent of organ damage correlates
Communication via the cytokine network
A role for PMN in the induction and quality of antigen-specific T cell response was deduced from experimentally induced infection in mice. Depletion of PMN, for example, induced a non-protective TH2 immune deviation in response to infection with Candida albicans or Legionella pneumophila in mice 26, 27. IL-12, which is produced by PMN in response to infection, appears to be decisive for the induction of the TH1 response in mice, which in turn would result in a protective immune response to the
PMN as immunosuppressive cells
Although the evidence is growing that PMN can participate in antigen presentation, and hence could have an impact on the induction and the quality of the T cell response, more recent data indicate that PMN can also have immunosuppressive functions. Various mechanisms have been identified, and their relevance has been studied in physiological and pathological conditions, i.e. in pregnancy and cancer. How can PMN suppress the adaptive immune response? PMN are equipped with effector systems that
PMN and T cells in tumours
Nearly 15 years ago, it was reported that the depletion of granulocytes in a murine tumour model can inhibit tumour growth in T cell-deficient nude mice and lead to complete tumour rejection in normal mice with a functional adaptive immune system [74]. A reasonable explanation is that PMN promote tumour growth by down-regulating the immune response directed towards the tumour. Indeed, the immunosuppressive potential of PMN has recently been demonstrated in various murine tumour models and in
Can we resolve the paradox of the PMN?
PMN are crucial for an efficient host defence, and as antigen-presenting cells they probably also affect the quality and the magnitude of the adaptive immune response. Thus, at first glance, it appears contradictory that PMN are able to suppress T cell responses. A possible explanation is that the PMN population is versatile and adapts to its microenvironment: in the case of acute infection, for example, infiltrating PMN activate and release bactericidal and potential cytotoxic mediators,
Concluding remarks
PMN and T cells co-localize at inflammatory sites where they have multiple interactions and mutual activation. The concept of different immune compartments, namely the innate and adaptive immune response, may be outdated. Although it is true that PMN share many features with their archaic precursors found in species that lack an adaptive immune response, the “modern type” PMN has apparently evolved further and has acquired molecules that allow interaction with cells of the adaptive immune
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