Lymphoproliferative response

T-cell Lymphoproliferation Response. This assay is analogous to the B-cell lymphoproliferative response assay described in the preceding paragraph. Thus, this assay is also classified as a Tier I test by the NTP and as an Expanded Type I test in the revised draft of the Redbook. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

Studies in animals, mostly intermediate-duration studies in rodents, indicate that a variety of immunological parameters such as spleen and thymus weights, antibody production, and lymphoproliferative responses can be affected by treatment with commercial PBB mixtures. The only chronic study found increased splenic hematopoiesis in mice, but no histological changes in the spleen, thymus, or lymph nodes of rats. It is... 

Cell-mediated immunity Lymphoproliferative response T cell mitogens (Con A and... 

The immune status of children exposed to 2,3,7,8-TCDD in the Seveso incident was also examined (Mocarelli et al. 1986). The group consisted of 44 children, 20 of whom had chloracne. The results of the testing showed no abnormalities in serum immunoglobulin concentrations, levels of circulating complement, or lymphoproliferative responses to T- and B-cell mitogens. However, a different cohort of... 

TCDD-exposed children examined 6 years after the explosion showed a significant increase in complement protein levels, which correlated with the incidence of chloracne (Tognoni and Bonaccorsi 1982). The children also had increased numbers of peripheral blood lymphocytes and increased lymphoproliferative responses. No specific health problems were correlated with exposure to... 

Steger, K. K., Valentine, P. J., Heffron, F., So, M., and Pauza, C. D. (1999), Recombinant, attenuated Salmonella typhimurium stimulate lymphoproliferative responses to SIV capsid antigen in rhesus macaques, Vaccine, 17, 923-932. 

Riley EM, MacLennan C, Wiatkowski DK, Greenwood BM. Suppression of in-vitro lymphoproliferative responses in acute malaria patients can be partially reversed by indomethacin. Parasite Immunol. 1989 11 509-517. 

The immune response to mercury exposure is complex, depending in part on the dose of mercury and the genetic characteristics of the exposed population (see Section 2.4). Administration of 14.8 mg Hg/kg/day as mercuric chloride to B6C3F, mice 5 days a week for 2 weeks resulted in a decrease in thymus weight (NTP 1993), suggesting immune suppression. However, a 2-week exposure to 0.7 mg Hg/kg/day as mercuric chloride in the drinking water resulted in an increase in the lymphoproliferative response after stimulation with T-cell mitogens in a strain of mice particularly sensitive to the autoimmune effects of mercury (SJL/N) (Hultman and Johansson 1991). In contrast, a similar exposure of a strain of mice (DBA/2) not predisposed to the autoimmune effects of mercury showed no increase in lymphocyte proliferation. 

A significant suppression of the lymphoproliferative response to T-cell mitogens, concanavalin A, and phytohemagglutinin was observed in male B6C3Fj mice administered 2.9 or 14.3 mg Hg/kg/day as mercuric chloride in drinking water for 7 weeks (Dieter et al. 1983). A significant decrease in the weight... 

In BALB/c mice administered a diet containing 0.5 mg Hg/kg/day as methylmercury for 12 weeks, the thymus weight and cell number decreased by 22 and 50%, respectively, compared to the control group (Ilback 1991). The natural killer cell activity was reduced by 44 and 75% in the spleen and blood, respectively. However, the lymphoproliferative response in the spleen increased at this dose of mercury. 

Dhib-Jalbut, S., Gogate, N., Jiang, H., Eisenberg, H., and Bergey, G., Human microglia activate lymphoproliferative responses to recall viral antigens, J. Neuroimmunol., 65, 67, 1996. 

Khalfoun B. Thibault G, Lacord M, Gruel Y, Bardos P, Lebranchu Y. Docosahexaenoic and eicosapentaenoic acids inhibit lymphoproliferative responses in viho but not the expression of T cell surface activation markers. Scand J Immunol 1996 43 248-256. 

The first patient treated with a thymic factor was a 4-year-old girl with thymic hypoplasia and abnormal immunoglobulin synthesis (Wara et al, 1975 Wara, 1983). She was treated with TF5 at a dose of 20 mg/kg/week for a total of 33 months. After 1 month of thymosin therapy, she had conversion of delayed hypersensitivity skin tests as well as an increase in absolute lymphocyte count. In addition, T cell percentages increased from 10 to 60% and serum immunoglobulin levels increased from 220 to 1220 mg/dl. However, no effects were seen on T cell functions in lymphoproliferative responses to T cell mitogens or in MLR. The patient s clinical condition improved with a decrease in the number and severity of infections and diarrhea. She has continued off therapy and appears healthy at age 13. This initial success prompted the many subsequent therapeutic attempts with a variety of thymic preparations. 

To find out if the concurrent use of trimetazidine and ciclosporin was associated with any adverse effects, 12 kidney transplant patients taking ciclosporin were given trimetazidine 40 mg twice daily for 5 days. No changes in the pharmacokinetics of the ciclosporin were seen, and there were no alterations in interleukin-2 concentrations or soluble interleukin-2 receptors. An associated study by the same group of workers using two models (the lymphoproliferative response of normal human lymphocytes to phytohaemagglutinin and a delayed mouse hypersensitivity model) similarly found that trimetazidine did not interfere with the effects of ciclosporin. It was concluded on the basis of these two studies that the concurrent use of ciclosporin and trimetazidine need not be avoided. 

On the other hand, there is no evidence that oral administration of Echinacin can result in an excessive lymphoproliferative response. The study on marathon runners involved oral treatment for 12 weeks, without a discernible adverse effect on lymphocyte counts. Even when given by various routes of administration to patients with relapsing candidiasis for ten weeks, no adverse immunological overstimulation was observed [23]. The lack of mutagenic activity of the isolated polysaccharide from . purpurea further supports the tolerability of the product [41]. In in vitro... 

The interaction between dietary PUFA and vitamin E levels was discussed recently by Sheffy and Shultz (1979). They reported that dogs fed diets high in PUFA but deficient in vitamin E and selenium rapidly developed a severely depressed lymphoproliferative response to mitogens. Vitamin E completely restored the response. The effect appears to be connected to preventing peroxidation of... 

---