Ontogeny of IgA(+) cells in lamina propria: effects of sympathectomy.

The effect of chemical sympathectomy on the ontogeny of the IgA(+) cells in the intestinal LP was examined in weanling rats. Ablation of the peripheral sympathetic nerve terminals using 6-hydroxydopamine (6-OHDA) on days 14 and 17 was associated with an increase in the number of IgA(+) and IgM(+) cells in the intestinal LP at 28, 30 and 35 days of age. Despite the precocious development of Ig-containing cells in the gut, the specific intestinal immune response to ovalbumin (OVA), induced by IP priming with OVA at 30 days of age and boosting ID 14 days later, was not altered by 6-OHDA treatment, with no difference observed in the numbers of total AOCC or IgA(+)/AOCC in the LP of treated, compared to control animals. The results presented in this study suggest that sympathetic innervation is an influential factor in the ontogeny of IgA(+) cells populating the intestinal lamina propria, although no functional significance in terms of the specific local response to a new antigen was detected using the immunisation model described here.

Sympathectomy abrogates immunodeficiency associated with protein-energy malnutrition.

The role of the sympathetic nervous system in the immune deficiency developed in protein-energy malnutrition (PEM) was investigated by assessing the effects of sympathectomy on the intestinal immune response of rats subject to prenatal or postnatal malnutrition. Chemical sympathectomy increased the number of IgA+ cells migrating into the intestinal lamina propria of control animals, but this effect was abrogated in rats malnourished during their perinatal stage. The method by which perinatal malnutrition was achieved influenced the magnitude of the effect on serum IgA levels with malnutrition during lactation having a more pronounced depressive effect on IgA than malnutrition during gestation. In experiments in which animals were intestinally immunised with ovalbumin (OVA) the mucosal immune response was reduced in non-sympathectomised malnourished (MN) animals and a lower level of anti-OVA IgA was detected in serum. However, in sympathectomised animals, there was no difference between MN animals and controls in the intestinal and humoral immune responses. The preliminary evidence presented in this paper strongly supports a role for the noradrenergic neurotransmitter system in the immunodeficiency developed during PEM.

The role of sympathetic innervation of the gut in regulating mucosal immune responses.

The effects of chemical sympathectomy on the mucosal compartments of the immune system were examined in adult rats. Ablation of the sympathetic nervous system using 6-hydroxydopamine in recipient animals reduced the migration into Peyer's patches and mesenteric lymph nodes (MLN) of adoptively transferred cells from MLN of normal donors. The mucosal immune response to ovalbumin (OVA), assessed by enumeration of anti-OVA antibody containing cells (AOCC) in the lamina propria after intestinal immunisation, was reduced in animals sympathectomized prior to immunization. In order to identify whether this reduction in AOCC response in intestinally immunized sympathectomized animals was due to a defect in migration of AOCC precursors to the intestinal lamina propria, the effect of chemical sympathectomy on the appearance of AOCC in the gut of immunized animals after adoptive transfer of AOCC precursors was investigated. The IgA-specific AOCC response was significantly reduced in sympathectomized recipients compared to the control group. Taken together these results demonstrate that the peripheral sympathetic nervous system influences the migration and accumulation in vivo of both naive and memory/effector lymphocytes in mucosal lymphoid tissues.

IgA B lymphocytes and subpopulations of T lymphocytes in the intestinal villi of immunodeficient Wistar rats.

The aim of this study is to characterize intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), as well as IgA B cells in the intestinal villi of the small intestine of rats which were fed a protein free diet (PF) and of those which were refed a 20% casein diet for 21 days (R21). Age matched control groups are also analyzed. T cell subsets and IgA-B cells were studied in tissue sections by the immunofluorescence technique. Lamina propria (LP) of the small intestine of the PF group were almost devoid of IgA-B cells; in the R21 group, the number of IgA-B cells was significantly diminished, when compared to the control group. The number of LPL in R21 group was not significantly different from the control group. W3/25+ (CD4) IEL diminished significantly in the intestinal villi of R21 group, while OX8+ (CD8) and OX22+ (CD45R) IEL were significantly increased when compared to the control group. These results indicate that: 1) Protein deficiency provokes an impairment of IgA-B cell terminal differentiation. 2) There is repopulation of LP by T cells in the R21 group. 3) The increased number of OX8+ (CD8) and OX22+ (CD45R) IEL might permit induction of intestinal delayed type hypersensitivity, thereby abrogating oral tolerance of systemic delayed type hypersensitivity.

[The lymphoid system and protein deficiency. Differentiation in the thymus and Peyer's patches]. / Sistema linfoide y deficiencia proteica. Diferenciación en timo y placas de Peyer.

A: Thymuses from protein deprived rats present: 1) a significant decrease in the absolute number of thymic cells bearing the CD5 phenotype (OX19+), as well as Thy 1.1 (OX7+). The predominant cell population was the one containing TdT (terminal deoxynucleotidyl transferase) as a sole marker: 2) in severely protein deprived rats followed by refeeding during 9 and 21 days, the existence of a small population of cells containing TdT as a sole marker. The TdT+W3/13+ cell population was restored but the CD4+ subpopulation (W3/25+) exists in lower numbers than in the age-matched controls. B: Severe protein deficiency at weaning, led to the presence in the Peyer's patches of very immature B-cells mostly c mu+OX7s mu-. Protein refeeding reinitiated the differentiation process as follows: 1) c mu+OX7+s mu- c mu-OX7-s mu+ as in the normal Peyer's patches; 2) however, switching of sIgM to sIgA-bearing cells was altered; 3) a low absolute number of W3/13+ and W3/25+ T-cells (CD4+) was found. C: Oral tolerance to dextrin evolved due to antigen specific CD8+ T-cells (found in Peyer's patches, mesenteric lymph nodes and spleen) and could be transferred to normal recipients.

Sistema linfoide y deficiencia proteica. Diferenciación en timo y placas de Peyer. / [The lymphoid system and protein deficiency. Differentiation in the thymus and Peyers patches]

A: Thymuses from protein deprived rats present: 1) a significant decrease in the absolute number of thymic cells bearing the CD5 phenotype (OX19+), as well as Thy 1.1 (OX7+). The predominant cell population was the one containing TdT (terminal deoxynucleotidyl transferase) as a sole marker: 2) in severely protein deprived rats followed by refeeding during 9 and 21 days, the existence of a small population of cells containing TdT as a sole marker. The TdT+W3/13+ cell population was restored but the CD4+ subpopulation (W3/25+) exists in lower numbers than in the age-matched controls. B: Severe protein deficiency at weaning, led to the presence in the Peyers patches of very immature B-cells mostly c mu+OX7s mu-. Protein refeeding reinitiated the differentiation process as follows: 1) c mu+OX7+s mu- c mu-OX7-s mu+ as in the normal Peyers patches; 2) however, switching of sIgM to sIgA-bearing cells was altered; 3) a low absolute number of W3/13+ and W3/25+ T-cells (CD4+) was found. C: Oral tolerance to dextrin evolved due to antigen specific CD8+ T-cells (found in Peyers patches, mesenteric lymph nodes and spleen) and could be transferred to normal recipients.