Immunological cells markers in the human neurocysticercosis

IMMUNOLOGICAL CELLS MARKERS IN THE HUMAN NEUROCYSTICERCOSIS (ABSTRACT)^*. THESIS. SÃO PAULO, 2001.

EDNÉIA CASAGRANDA BUENO^**

The biological interaction of parasite-host involving in the neurocysticercosis (NC) is complex for the parasite antigens in different stages of evolution and the individual genetic variations interfering on the host response, will help to understand the dynamic of the parasite survival and the host defense mechanisms.

To contribute for the elucidation of the mechanism related to the parasite-host interaction in NC, immune response markers of 23 NC patients were studied in different stages of the disease: immunophenotyping (T cell, helper T cell, cytotoxic T cell, B cell, natural killer cells, HCAM and ICAM adhesion molecules and early activation marker CD69) of the cerebrospinal fluid (CSF) and peripheral blood; mononuclear cell proliferation in vitro after antigen-specific stimulation; and quantification of citokines (IL-1b, IL-4, IL-6, IL-10, IL-12, TNF-a) and adhesion molecules (ICAM and VCAM) produced in the lymphoproliferation assay.

The mean expression of the early activation marker CD69, in all kinds of cells identified in the samples of peripheral blood and in the CSF of NC patients was higher than the control group. The difference was always higher than 50% in CSF samples, indicating cell activity in the host as a response to the parasite.

Although there is no statistical difference (p = 0.068 the lower value), the CSF samples have shown higher percentages of T cells (70.9%), helper T cells (54.4%), B cells (15.8%) and natural killer cells (10.2%) when compared to the samples of peripheral blood (respectively 68.9%; 49.5%; 4.4% and 5.1%), suggesting local action of the defense system involved in the NC.

Patients with active NC have shown, in general, increasing of the cytotoxic T cells in peripheral blood samples (44.5%) and CSF (33.2%) when compared to the control group (respectively 36.0% and 26.9%), indicating the involvement of cytotoxic and suppressor mechanism in immunopathogenic process of the NC.

The mononuclear cells of NC patients have shown antigen-specific suppression in vitro (stimulation index, SI < 2.5) when compared to those of the control group. This suppression was more intense in samples of patients having no alterations in the image examination (SI £ 2.2) and having cysts in degeneration process (SI £ 2.3), and less intense in samples of patients with different evolution forms (SI £ 2.7) and of patients having calcified cysts (SI £ 6.5).

The suppression observed in NC seems to be induced by the parasite antigen components as it was observed in excretion and secretion antigens part of the vesicular fluid of T. crassiceps (VF-Tcra), that inhibited the cellular immune response induced by the mitogens phytohemagglutinin (98%), concanavalin A (99%) and pokeweed (98%). This suppression seems also to be related to the predominance of Th2 response (IL-4, IL-6, IL-10), as it can be observed in the citokines quantification in the supernadant of the lymphoproliferation assay stimulated by VF-Tcra antigen.

The presence of antibodies was observed independently of the response obtained in the lymphoproliferation assay (65% of the positive SI patients and 35% of those with negative SI), suggesting that the activity of the humoral immune response has occurred since the beginning of the infection.

The adhesion molecules were detected in NC patients, in values higher than those found in the control group, for both soluble form of ICAM and VCAM in culture of peripheral blood mononuclear cells after antigen-specific stimulation in vitro (respectively 46% and 60% of the patients) and in transmembrane form of HCAM and ICAM in cells of peripheral blood samples (71.4% and 85.7% of the patients) and CSF samples (55.5% and 88.8% of the patients), indicating that these molecules act in the cell migration related with the immune response in NC.

Patients with cysts in degeneration have shown mainly Th1 citokines, while the other evolution phases have shown a mixed profile Th1/Th2 (IL-1b, IL-4, IL-6, IL-10, IL-12 and TNF-a) with predominance of Th2 (IL-4, IL-6, IL-10) in the majority of them (65%), demonstrating the heterogeneity of the immune response in NC.

The production of the TNF-a in 75% of the samples of NC patients also indicates that the cytotoxic mechanism is involved in the NC immunopathogenic process.

KEY WORDS: neurocysticercosis, immune response, flow cytometry, lymphocyte proliferation, cytokine.

**Address: UNIVALI - Curso de Farmácia, Rua Uruguai 458, 88302-202 Itajaí SC, Brasil.

*

Marcadores imunológicos celulares na neurocisticercose humana (Resumo). Tese de Doutorado, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo (Área: Análises Clínicas). Orientadora: Adelaide José Vaz.

Publication Dates

• Publication in this collection
  11 Apr 2002
• Date of issue
  Mar 2002