Nerves and neuropeptides in the regulation of mucosal immunity.
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Biomedical subjects
K Croitoru
Publications and source records attributed to K Croitoru.
Neuroendocrine regulation of mucosal immunity.
In view of the extensive innervation of the gastrointestinal tract, including the mucosa, and the high number of immune effector cells present in this tissue, we have studied the effects of certain neurotransmitters on immune responses. We have concentrated on the effects of the neuropeptides substance P (SP), somatostatin (SOM) and vasoactive intestinal peptide (VIP). We have found that SP causes an increase in the proliferation of Peyer's patch lymphocytes as well as immunoglobulin (especially IgA) synthesis, when compared to splenic cells; and that there is a greater expression of SP receptors on lymphocytes derived from Peyer's patches compared to the spleen, without a significant difference in the expression between subsets of T and B cells. Furthermore, we have shown that intraepithelial leukocytes (IEL) show significantly increased cytotoxic activity following incubation with SP; whereas splenic lymphocytes were not stimulated in the same system. The effects of SOM where bi-directional depending upon the concentration employed but in general, SOM was inhibitory, in terms of proliferation, as was VIP. Although many more experiments are required to prove a physiological significance for the results that we have obtained, and to examine the whole gamut of neurotransmitters, we suggest that neuroendocrine regulation may play an important part in mucosal immunity.
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Leukocytes in the intestinal epithelium: an unusual immunological compartment revisited.
Intraepithelial lymphocytes (IEL) are characterized by significant heterogeneity in morphology, surface antigen expression, and function. Although IEL can express T cell markers including the T cell receptor (TcR), their relationship to peripheral T cells is not clear. The finding of IEL in athymic nude mice first suggested that a number of IEL may be thymic-independent. The identification of the gamma/delta TcR heterodimer on IEL further suggested that these cells are part of a distinct population of epithelial-associated lymphocytes, many of which express the gamma/delta TcR. We review the nature of the V gamma gene usage in IEL and highlight the differences between different gamma/delta T cell populations. The thymic independent nature of these gamma/delta cells is discussed and compared to that of the alpha/beta TcR expressing IEL. The finding that some alpha/beta IEL can develop independent of thymic processing suggests that IEL are characterized by a unique collection of T cells that may undergo differentiation within the intestinal compartment. The ability to distinguish T-dependent from T-independent IEL raises the possibility of identifying the functional nature of these two IEL lineages. We propose that the ability of IEL to potentially undergo repertoire selection in the intestine could allow for the development of mucosal T cells uniquely adapted to function in this environment.
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