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Immune development in un-weaned pigs

Immune development was studied in conventional (farm reared) and isolator (SPF) reared piglets to 28 d of age. Pairs of farrowing sows were selected from a commercial pig farm and at 24 hours, half of each litter was removed from sow and transferred to an SPF isolator. The other half of the litter remained with the sow and the piglets were not given access to creep feed. The isolator piglets were fed a bovine-based milk replacer on an hourly-based cycle. Piglets (n=6 per group) from both experimental groups were killed at 2, 5, 12, 20 and 28 days of age. Tissue samples were collected from the small intestine, spleen and mesenteric lymph node for phenotypic analysis, by flow cytometry and immunohistology, and functional analysis, by in vitro cytokine production and cell proliferation/survival analysis.

Gross morphological examination of the intestines from isolator and farm reared showed that those from the farm-reared animals were thicker but this was not reflected in any difference in the number of immune cells isolated.

Work carried out under the current project has confirmed the progressive nature of this developmental process, and highlighted that lack of maturity of the pig gut immune at ages that are commonly used in European weaning practices. In the present study the use of flow cytometry for the characterisation of lamina propia cells has enabled us to identify the sub-populations involved. Whilst CD3+ T cells dominated throughout the first 28 days of life, there were significant changes in the major sub-populations.

In pigs less than 12 days the lamina propria is dominated by T cells expressing either low levels of CD8 (CD8low) or negative for CD4 and CD8 (CD4-CD8- double negative). Interestingly from 12 - 28 days CD4+CD8+ cells dominate and this cell type has been associated with anti-viral activity (Saalmuller et al .1999). The CD8low cells also carried initially high levels of CD25 and low levels of CD45RC, representing a recently activated cell population. However, unlike the CD4 cell population, although CD25 was lost by day 12, low levels of CD45RC remained on this T cell subset.

Unfortunately, for technical reasons, a further phenotypic characterization was not possible for the CD4-CD8- negative cell type. Other work (see below) demonstrated that LP T cells were capable of IL-2 secretion until day 21, this capacity was subsequently lost, whereas IL-4 secretion continued. From this time point onwards, the lamina propria environment was characterized by resting cells of advanced memory status, secreting IL-4 and not Il-2, possibly regulated or regulating or both.

A further unusual cell type characteristic of the gut of very young pigs was a CD2+CD3- cell population, expressing uniformly high levels of CD25. The function and identity of these CD2+CD3-CD25+++ cells is as yet unknown, other work with appropriate markers (not shown) appears to preclude their identity as NK or B cells. However, their phenotype may be consistent with the existence of extra-thymic T cell development in the pig gut.

In general, polyclonal T cell activation of both spleen and lamina propria cells resulted in decreased numbers of CD4+ single positive cells and increased numbers of CD4+CD8+ double positive cells, consistent with induced expression of CD8aaon activated CD4+ cells.

The present study describes of antigen presenting cell populations during the first four weeks of life. The results showed that there were significant changes in the myeloid subsets with age, with a loss of CD14+ and increase in CD16+ and MHC II+. Interestingly even during this early stage there were clear interactions between CD16+MHC II+ and CD14+CD16+MHC II+ cells and MHC II+ and endothelium. These results would strongly indicate the potential for cellular cooperation within the lamina propria at this time and might highlight a possible mechanism whereby the organisation of lamina propria immune cells is established.

The results have shown that there are significant differences in the cell populations found in the intestinal lamina propria of young (less that 28 days) as opposed to older piglets. The results strongly support the conclusion that at ages commonly used in European pig weaning practices, the piglets immune system may not be sufficiently developed to respond to the challenges of weaning. This would suggest that either a later weaning age should be adopted or we should seek to enhance the development of the piglets' mucosal immune system.

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UNIVERSITY OF BRISTOL
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