Browsing by Author "Ramić, Zorica (6603943950)"

Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed. © 1992.

Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed. © 1992.

T cell subsets in the peripheral blood, draining lymph node (DLN) and spinal cord lesions were analysed after the induction of experimental autoimmune encephalomyelitis (EAE) in susceptible (DA) and relatively resistant (AO) rats. In DA rats, a significantly higher number of CD4+ cells were generated in the DLN, in response to both nervous tissue antigens and complete Freund's adjuvant (CFA), compared to AO rats. In the peripheral blood of DA rats, the percentage as well as absolute number of CD4+ cells increased in the preclinical phase of EAE, but declined as the disease developed. The percentage of CD8+ cells decreased in both these phases of EAE. In resistant AO rats, however, there were no significant changes in the T lymphocyte subset percentage after EAE induction, although the absolute number of peripheral blood CD4+ cells again increased in the preclinical stage of EAE. In the CFA-treated control DA rats, the absolute number of CD4+ cells was increased in the preclinical phase. However, no decline comparable to that seen in diseased animals followed. It is concluded that the generation of CD4+ cells in response to this antigen is strain specific and, since the cells are released into the circulation, will affect the balance between the T cell subsets in the peripheral blood during the development of EAE. © 1990.

T cell subsets in the peripheral blood, draining lymph node (DLN) and spinal cord lesions were analysed after the induction of experimental autoimmune encephalomyelitis (EAE) in susceptible (DA) and relatively resistant (AO) rats. In DA rats, a significantly higher number of CD4+ cells were generated in the DLN, in response to both nervous tissue antigens and complete Freund's adjuvant (CFA), compared to AO rats. In the peripheral blood of DA rats, the percentage as well as absolute number of CD4+ cells increased in the preclinical phase of EAE, but declined as the disease developed. The percentage of CD8+ cells decreased in both these phases of EAE. In resistant AO rats, however, there were no significant changes in the T lymphocyte subset percentage after EAE induction, although the absolute number of peripheral blood CD4+ cells again increased in the preclinical stage of EAE. In the CFA-treated control DA rats, the absolute number of CD4+ cells was increased in the preclinical phase. However, no decline comparable to that seen in diseased animals followed. It is concluded that the generation of CD4+ cells in response to this antigen is strain specific and, since the cells are released into the circulation, will affect the balance between the T cell subsets in the peripheral blood during the development of EAE. © 1990.

Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified in complete Freund’s adjuvant (CFA). We provide evidence that 6, 6′-trechalose dymicolate (TDM) incorporated in incomplete Freund’s adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. Tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only. © 1988 S. Karger AG, Basel.

Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified in complete Freund’s adjuvant (CFA). We provide evidence that 6, 6′-trechalose dymicolate (TDM) incorporated in incomplete Freund’s adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. Tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only. © 1988 S. Karger AG, Basel.

A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1av1) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE. © 1992.

A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1av1) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE. © 1992.

Background: There is an apparently increased tendency toward infections in patients with Gaucher disease, possibly due to defective neutrophil function rather than a decreased neutrophil count. Since macrophages are the main cell type affected in Gaucher disease, our aim was to determine the contribution of these cells to the susceptibility of Gaucher patients to infection by studying the respiratory burst capacity of peripheral blood monocytes. Methods: The study was performed in eleven Gaucher type 1 patients and eleven sex and age matched control subjects by measuring peripheral blood monocytes' respiratory burst capacity using flow cytometry. The respiratory burst capacity was measured as dihydrorhodamine-123 median fluorescence in patients and respective controls. Results: There was no statistical difference in the median fluorescence among the patients and respective controls (p>0.05) after phorbol 12-myristate 13-acetate stimulation. Also, statistical difference was not reached among patients treated with enzyme replacement therapy at the time and those untreated. Conclusions: Flow cytometry might represent a more accurate and more reliable measure of respiratory burst compared to the methods of other researchers. Respiratory burst disturbance in monocytes does not seem to contribute to increased susceptibility to infection in Gaucher patients.

Background: There is an apparently increased tendency toward infections in patients with Gaucher disease, possibly due to defective neutrophil function rather than a decreased neutrophil count. Since macrophages are the main cell type affected in Gaucher disease, our aim was to determine the contribution of these cells to the susceptibility of Gaucher patients to infection by studying the respiratory burst capacity of peripheral blood monocytes. Methods: The study was performed in eleven Gaucher type 1 patients and eleven sex and age matched control subjects by measuring peripheral blood monocytes' respiratory burst capacity using flow cytometry. The respiratory burst capacity was measured as dihydrorhodamine-123 median fluorescence in patients and respective controls. Results: There was no statistical difference in the median fluorescence among the patients and respective controls (p>0.05) after phorbol 12-myristate 13-acetate stimulation. Also, statistical difference was not reached among patients treated with enzyme replacement therapy at the time and those untreated. Conclusions: Flow cytometry might represent a more accurate and more reliable measure of respiratory burst compared to the methods of other researchers. Respiratory burst disturbance in monocytes does not seem to contribute to increased susceptibility to infection in Gaucher patients.