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T-CELLS
Autistic children have been shown to exhibit abnormal T cell activation (Warren et al, 1995).
Children with autism had a lower percentage of helper-inducer cells and a lower helper:suppressor ratio, with both measures inversely related to the severity of autistic symptoms (Denney et al, 1996).
Endocrine studies on rats have shown identical effects in hypothyroid rats, and T3 treatment proven beneficial (Pacini et al, 1983) . Animals treated with high doses of T3 for 17 days did not develop any alteration either in the proportions or in the ratio of helper/suppressor T cells. Results suggested that hypothyroidism but not hyperthyroidism alters the normal balance between helper and suppressor T cells in rats (Pacini et al, 1983).
Human lymphocytes are known to play a critical role in autoimmune diseases both by producing antibodies and by participating in lymphokine-cellular interactions. TSH may be secreted by human lymphocytes and a specific, authentic TSH receptor is present on the surface of these cells (Francis et al, 1991). [TSH and TSH receptor may play a vital role in modulating local lymphokine activation of T and B cells, both in normal conditions and in autoimmune thyroid disease. ]
Autistic subjects have reduced numbers of CD4+ helper T cells (Yonk et al, 1990; Warren et al, 1990).
CD4 T cells are a critical subpopulation of regulatory T-lymphocytes involved in the induction of most immunological functions.
10-20% of CD4+8- and CD4-8+ lymph node T cells express the TSH receptor, which is exclusively associated with CD45RB (high) cells (Bagriacik et al, 2000).
G q/11: The T3-Ti complex appears to play a central role in the activation of T cells by antigens and mitogens. Wheat germ agglutinin (WGA) is a unique lectin which inhibits T cell proliferation induced by mitogens, but it also induces marked IL 2 production by peripheral blood T cells (Yachie et al, 1987).
It activates human T lymphocytes by stimulation of phosphoinositide hydrolysis (Clevers et al, 1986).
The CNS is enriched in phosphoinositide-specific phospholipase C (PLC) and in the G proteins linked to its activation. Retinoic acid-mediated differentiation of NT2 precursor cells to the neuronal phenotype resulted in five- to 15-fold increases in the expression of PLC-beta1, PLC-beta4, and Galpha(q/11) (the prime G protein activator of these isozymes) (Novak et al, 2000).
NT2-N cells -> a well characterized model system for CNS neurons.
- Butler et al (1990) gave fluoride amounts at a concentration range similar as what children ingest from supplements and found that intragastric fluoride causes increases in the size and cellularity of the Peyer's patches and mesenteric lymph nodes as well as the number of plasma cells secreting IgG and IgA antibodies to ovalbumin (OA) given in their drinking water. Rats ingesting NaF and fed OA showed a significant increase in surface immunoglobulin expression on lymphocytes from the Peyer's patches and mesenteric lymph nodes. The frequency of CD4+ T cells in these lymphoid tissues was elevated while that of CD8+ T cells was significantly decreased. In separate experiments, rats parenterally immunized with myelin basic protein (MBP) and fed NaF twice weekly, had significantly elevated serum IgG antibody activity to MBP compared to similarly immunized rats not receiving NaF.***** The authors concluded that the supplemental fluoride prescribed for infants and especially that which is inadvertently ingested by children and adults given fluoride gels, is within the concentration range of that which produced the effects which was observed in rats. "The adjuvant effect we describe thus has relevance for fluoride therapy worldwide." (Butler et al, 1990)
Balabolkin et al (1995) study the thyroid and immune statuses in workers continuously exposed to fluorine. The examinees with euthyroid condition had immune disorders with an allergic tendency (increased number of B-lymphocytes, immunoglobulins A). In workers with subclinical hypothyrosis (T3 reduced in 51%), the immune alterations were more evident, T-lymphocytes count rose, but their functional activity declined, indicating impaired cooperation of immunocytes as a result of imperfect control under low concentrations of T3.
These alterations were also evident in the recent first-ever investigation into the general health conditions of children afflicted with dental fluorosis (Miroshnychenko, 2000).
See also: IL-2, Interferon
Gq/11: 80 references
phosphoinositide+hydrolysis+G+q+11 (24 references) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=4&db=m&term=phosphoinositide+hydrolysis+G+q+11
phosphoinositide+hydrolysis+G+q+11 (57 references) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=4&db=m&term=phosphoinositide+G+q+11
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Bagriacik EU, Klein JR - "The thyrotropin (thyroid-stimulating hormone) receptor is expressed on murine dendritic cells and on a subset of CD45RBhigh lymph node T cells: functional role for thyroid-stimulating hormone during immune activation" Immunol 164(12):6158-65 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10843665&form=6&db=m&Dopt=r
Balabolkin MI, Mikhailets ND, Lobovskaia RN, Chernousova NV - "The interrelationship of the thyroid and immune statuses of workers with long-term fluorine exposure" Ter Arkh 67(1):41-2 (1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7709355&form=6&db=m&Dopt=r
Butler JE, Satam M, Ekstrand J - "Fluoride: an adjuvant for mucosal and systemic immunity" Immunol Lett 26(3):217-20 (1990) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1707853&form=6&db=m&Dopt=r
Clevers HC, de Bresser A, Kleinveld H, Gmelig-Meyling FH, Ballieux RE - "Wheat germ agglutinin activates human T lymphocytes by stimulation of phosphoinositide hydrolysis" J Immunol 136(9):3180-3 (1986) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3007612&form=6&db=m&Dopt=r
Denney DR, Frei BW, Gaffney GR. - "Lymphocyte subsets and interleukin-2 receptors in autistic children" J Autism Dev Disord 26(1):87-97 (1996) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&uid=8819772&Dopt=r
Francis T, Burch HB, Cai WY, Lukes Y, Peele M, Carr FE, Wartofsky L, Burman KD - "Lymphocytes express thyrotropin receptor-specific mRNA as detected by the PCR technique" Thyroid 1(3):223-8 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1824338&form=6&db=m&Dopt=r
Miroshnychenko O - Sosnivka FInal Report, ECOPRAVA Liev, under USAID SCIENTIFIC ASSESSMENT GRANT (2000)
Novak JE, Agranoff BW, Fisher SK - "Increased expression of Galpha(q/11) and of phospholipase-Cbeta1/4 in differentiated human NT2-N neurons: enhancement of phosphoinositide hydrolysis" J Neurochem 74(6):2322-30 (2000) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10820192&form=6&db=m&Dopt=r
Pacini F, Nakamura H, DeGroot LJ - "Effect of hypo- and hyperthyroidism on the balance between helper and suppressor T cells in rats" Acta Endocrinol (Copenh) 103(4):528-34 (1983) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6225290&form=6&db=m&Dopt=r
Warren RP, Yonk J, Burger RW, Warren WL - "DR-positive cells in autism: association with decreased plasma levels of the complement C4b protein" Neuropsychobiology 31(2):53-7(1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&uid=7760985&Dopt=r
Warren RP, Yonk LJ, Burger RA, Cole P, Odell JD, Warren WL, White E, Singh VK - "Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism" Immunol Invest 19(3):245-51 (1990) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2142123&form=6&db=m&Dopt=r
Yonk LJ, Warren RP, Burger RA, Cole P, Odell JD, Warren WL, White E, Singh VK - "CD4+ helper T cell depression in autism" Immunol Lett 25(4):341-5 (1990) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1979061&form=6&db=m&Dopt=r
Yachie A, Hernandez D, Blaese RM - "T3-T cell receptor (Ti) complex-independent activation of T cells by wheat germ agglutinin" J Immunol 138(9):2843-7 (1987) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=2952724&form=6&db=m&Dopt=r
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