TY  - CONF
AU  - Nacka-Aleksić, M.
AU  - Stojanović, M.
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/851
AB  - Introduction: It is suggested that impaired thymopoiesis in autoimmune diseases contributes to their perpetuation. To prove this hypothesis, influence of immunization for EAE on thymopoiesis and the putative thymic−dependent changes in the periphery were examined in susceptible (Dark Agouti, DA) and resistant (Albino Oxford, AO) rats. Methods: On the 13th day post−immunization, expression of differentiation/maturation markers of conventional T cells and regulatory CD4+Foxp3+CD25+ cells (nTregs) on thymocytes, their apoptosis and proliferation, frequency of recent thymic emigrants (RTEs) and CD28null cells in CD4+ and CD8+ peripheral blood lymphocytes (PBLs), and thymic expression and circulating levels of cytokines influencing thymus/thymopoiesis were investigated. Results: In rats of both strains increase in proinflammatory−cytokine circulating levels followed by thymic atrophy and changes at multiple thymocyte developmental points, leading to decreased number of the most mature CD4+ and CD8+ TCRaβhi thymocytes and frequency of RTEs among PBLs (as in chronobiological aging), was found. This was more prominent in DA rats. Consistently, compared with AO rats, in DA rats were found higher frequencies
of cytolitic CD28null cells (contributing to target tissue damage) among CD4+ PBLs and cytolitic granzyme B+ CD4+ T cells in spinal cord. Additionally, compared with non−immunized controls, DA rats exhibited greater decline in thymic nTreg generation (reflecting diminished thymic IL−7, IL−2 and IL−15 expression) than AO ones. Conclusions: The study suggests that differences in thymopoiesis, and consequently nTreg generation and CD4+CD28null cell frequency in the periphery, contribute to strain differences in EAE clinical presentation.
C3  - Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands
T1  - Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE
SP  - P.A2.03.06
UR  - https://hdl.handle.net/21.15107/rcub_intor_851
ER  - 

@conference{
author = "Nacka-Aleksić, M. and Stojanović, M. and Pilipović, Ivan and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: It is suggested that impaired thymopoiesis in autoimmune diseases contributes to their perpetuation. To prove this hypothesis, influence of immunization for EAE on thymopoiesis and the putative thymic−dependent changes in the periphery were examined in susceptible (Dark Agouti, DA) and resistant (Albino Oxford, AO) rats. Methods: On the 13th day post−immunization, expression of differentiation/maturation markers of conventional T cells and regulatory CD4+Foxp3+CD25+ cells (nTregs) on thymocytes, their apoptosis and proliferation, frequency of recent thymic emigrants (RTEs) and CD28null cells in CD4+ and CD8+ peripheral blood lymphocytes (PBLs), and thymic expression and circulating levels of cytokines influencing thymus/thymopoiesis were investigated. Results: In rats of both strains increase in proinflammatory−cytokine circulating levels followed by thymic atrophy and changes at multiple thymocyte developmental points, leading to decreased number of the most mature CD4+ and CD8+ TCRaβhi thymocytes and frequency of RTEs among PBLs (as in chronobiological aging), was found. This was more prominent in DA rats. Consistently, compared with AO rats, in DA rats were found higher frequencies
of cytolitic CD28null cells (contributing to target tissue damage) among CD4+ PBLs and cytolitic granzyme B+ CD4+ T cells in spinal cord. Additionally, compared with non−immunized controls, DA rats exhibited greater decline in thymic nTreg generation (reflecting diminished thymic IL−7, IL−2 and IL−15 expression) than AO ones. Conclusions: The study suggests that differences in thymopoiesis, and consequently nTreg generation and CD4+CD28null cell frequency in the periphery, contribute to strain differences in EAE clinical presentation.",
journal = "Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands",
title = "Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE",
pages = "P.A2.03.06",
url = "https://hdl.handle.net/21.15107/rcub_intor_851"
}

Nacka-Aleksić, M., Stojanović, M., Pilipović, I., Kosec, D.,& Leposavić, G.. (2018). Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands, P.A2.03.06.
https://hdl.handle.net/21.15107/rcub_intor_851

Nacka-Aleksić M, Stojanović M, Pilipović I, Kosec D, Leposavić G. Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE. in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands. 2018;:P.A2.03.06.
https://hdl.handle.net/21.15107/rcub_intor_851 .

Nacka-Aleksić, M., Stojanović, M., Pilipović, Ivan, Kosec, Duško, Leposavić, Gordana, "Immunization-induced thymic atrophy as a contributing factor in strain differences in rat susceptibility to EAE" in Abstracts of the 5th European Congress of Immunology - ECI 2018 - Amsterdam, The Netherlands (2018):P.A2.03.06,
https://hdl.handle.net/21.15107/rcub_intor_851 .

TY  - CONF
AU  - Bufan, B.
AU  - Arsenović-Ranin, N.
AU  - Dimitrijević, M.
AU  - Nacka-Aleksić, M.
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Stojanović, M.
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/850
AB  - Introduction: Considering sex bias in rheumatoid arthritis prevalence, influence of biological sex on the disease development in Dark Agouti rat collagen II (CII)−induced arthritis (CIA) model of the human disease was examined. Methods: Sex bias in CD4+ T cell responses in inguinal (draining the site of immunization in preclinical CIA) and popliteal (draining inflamed joints at the peak of CIA) lymph nodes (LNs) and mechanisms controlling their development were examined using flow cytometry and/or ELISA/qRT−PCR. Results: In both inguinal and popliteal LNs greater number of CD4+CD25+Foxp3− cells, presumably activated effector T cells, was found in females compared with males, and they exhibited greater CII−specific proliferation. Consistently, more IL−17+, IFN−γ+ and IL−17+IFN−γ+ T cells were retrieved from both inguinal and popliteal female rat LNs. Moreover, more GM−CSF+ and IL−17+IFN−γ+GM−CSF+ T cells were retrieved from female compared with male rat popliteal LNs. On the other hand, lower frequency of PD−1+ cells among CD4+CD25+Foxp3+ regulatory T cells (Tregs) from female popliteal and inguinal LNs suggested lower suppressive capacity of their Tregs. Additionally, from female rat popliteal LNs fewer Tregs were recovered. Furthermore, the number of regulatory LN B10 cells was lower in females. Moreover, compared with males, in females was shifted LN INF−γ+/IL−4+ T−cell ratio towards the former, and accordingly serum CII−specific IgG2a/IgG1 antibody ratio was shifted towards pathogenic IgG2a antibodies. Conclusion: The study suggests that a less efficient control of (auto)immune Th1/Th17 cell responses during CIA development contributes to sex bias in the susceptibility to CIA.
C3  - 5th European Congress of Immunology, Septembar 2-5, Abstract Book
T1  - Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis
SP  - P.C1.01.02
UR  - https://hdl.handle.net/21.15107/rcub_intor_850
ER  - 

@conference{
author = "Bufan, B. and Arsenović-Ranin, N. and Dimitrijević, M. and Nacka-Aleksić, M. and Kosec, Duško and Pilipović, Ivan and Stojanović, M. and Leposavić, Gordana",
year = "2018",
abstract = "Introduction: Considering sex bias in rheumatoid arthritis prevalence, influence of biological sex on the disease development in Dark Agouti rat collagen II (CII)−induced arthritis (CIA) model of the human disease was examined. Methods: Sex bias in CD4+ T cell responses in inguinal (draining the site of immunization in preclinical CIA) and popliteal (draining inflamed joints at the peak of CIA) lymph nodes (LNs) and mechanisms controlling their development were examined using flow cytometry and/or ELISA/qRT−PCR. Results: In both inguinal and popliteal LNs greater number of CD4+CD25+Foxp3− cells, presumably activated effector T cells, was found in females compared with males, and they exhibited greater CII−specific proliferation. Consistently, more IL−17+, IFN−γ+ and IL−17+IFN−γ+ T cells were retrieved from both inguinal and popliteal female rat LNs. Moreover, more GM−CSF+ and IL−17+IFN−γ+GM−CSF+ T cells were retrieved from female compared with male rat popliteal LNs. On the other hand, lower frequency of PD−1+ cells among CD4+CD25+Foxp3+ regulatory T cells (Tregs) from female popliteal and inguinal LNs suggested lower suppressive capacity of their Tregs. Additionally, from female rat popliteal LNs fewer Tregs were recovered. Furthermore, the number of regulatory LN B10 cells was lower in females. Moreover, compared with males, in females was shifted LN INF−γ+/IL−4+ T−cell ratio towards the former, and accordingly serum CII−specific IgG2a/IgG1 antibody ratio was shifted towards pathogenic IgG2a antibodies. Conclusion: The study suggests that a less efficient control of (auto)immune Th1/Th17 cell responses during CIA development contributes to sex bias in the susceptibility to CIA.",
journal = "5th European Congress of Immunology, Septembar 2-5, Abstract Book",
title = "Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis",
pages = "P.C1.01.02",
url = "https://hdl.handle.net/21.15107/rcub_intor_850"
}

Bufan, B., Arsenović-Ranin, N., Dimitrijević, M., Nacka-Aleksić, M., Kosec, D., Pilipović, I., Stojanović, M.,& Leposavić, G.. (2018). Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis. in 5th European Congress of Immunology, Septembar 2-5, Abstract Book, P.C1.01.02.
https://hdl.handle.net/21.15107/rcub_intor_850

Bufan B, Arsenović-Ranin N, Dimitrijević M, Nacka-Aleksić M, Kosec D, Pilipović I, Stojanović M, Leposavić G. Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis. in 5th European Congress of Immunology, Septembar 2-5, Abstract Book. 2018;:P.C1.01.02.
https://hdl.handle.net/21.15107/rcub_intor_850 .

Bufan, B., Arsenović-Ranin, N., Dimitrijević, M., Nacka-Aleksić, M., Kosec, Duško, Pilipović, Ivan, Stojanović, M., Leposavić, Gordana, "Sexual dimorphism in mechanisms controlling development of CD4+ T cell response in collagen-induced arthritis" in 5th European Congress of Immunology, Septembar 2-5, Abstract Book (2018):P.C1.01.02,
https://hdl.handle.net/21.15107/rcub_intor_850 .

TY  - CONF
AU  - Stojanović, M.
AU  - Živković, Irena
AU  - Inić-Kanada, A.
AU  - Petrušić, V.
AU  - Marinković, E.
AU  - Stojićević, I.
AU  - Dimitrijević, I.
PY  - 2012
UR  - http://intor.torlakinstitut.com/handle/123456789/711
AB  - Purpose/Objective: The hyperimmunization with tetanus toxoid
(TTd) induces protective TTd-specific as well as autoreactive b2-glycoprotein I (b2GPI)-specific immune responses in BALB/c mice. The
overall immune response characteristics, especially its pathogenic potential, depended on adjuvants applied prior and in combination with TTd. Beside structural homology between TTd and b2GPI, tolerance
toward b2GPI could be impaired by adjuvants acting as polyclonal
stimulators. In order to clarify the impact of adjuvants, phenotypic and
functional analyses of immune system cells within spleen were done
upon immunization completion.
Materials and methods: Non- or CFA-pretreated BALB/c mice were
immunized with TTd (3 · 100 lg/dose; 2-week intervals) mixed with
alum or 2.5M glycerol. Ex vivo analyses of CD3, CD4, CD8, CD19, CD
25, CD27 and mIgM expression on age-matched control and
immunized mice’s splenocytes were done by flow cytometry. Changes
in TLR2, TLR4 and TLR9 expression were assessed indirectly, by
measuring cytokine production, following in vitro stimulation of
splenocytes with appropriate agonist.
Results: TTd-immunization diminished CD27 expression on T cells
implying on their differentiation into potent effector cells. T cell
activation (increase in CD25 expression and the raise of percentage of
CD4+ CD8+ CD3+
) and B cell activation (rise in percentage of
CD19+ CD25+ cells and the increase of mIgM density) occurred in all
immunized mice, being more intensive in CFA-pretreated groups.
Irrespective to the applied immunization protocol, statistically significant rise in abundance of CD4- CD8- cells (often cited as cells having
suppressive potential) within T cell pool was registered too. Differences
in cytokines production (IL4, IL10, IFNc) registered upon in vitro
stimulation with peptidoglycan, LPS and CpG ODN implied on
context-dependant modulation of TLR2, TLR4 and TLR9 expression
on splenocytes.
Conclusions: TTd-hyperimmunization promoted concomitant rise in
abundance of activated cells and the cells that have suppressive
potential. This could be regarded as an attempt of the system to retain
control. Imbalance in percentages and activities between activated cells
and those having suppressive potential, highly influenced by the
context of TTd application, is most likely the cause for the observed
pathology appearance after TTd hyperimmunization.
PB  - Wiley
C3  - Immunology (Abstracts of the European Congress of Immunology, 5-8 September 2012, Glasgow, Scotland)
T1  - Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application
EP  - 423
IS  - s1
SP  - 423
VL  - 137
UR  - https://hdl.handle.net/21.15107/rcub_intor_711
ER  - 

@conference{
author = "Stojanović, M. and Živković, Irena and Inić-Kanada, A. and Petrušić, V. and Marinković, E. and Stojićević, I. and Dimitrijević, I.",
year = "2012",
abstract = "Purpose/Objective: The hyperimmunization with tetanus toxoid
(TTd) induces protective TTd-specific as well as autoreactive b2-glycoprotein I (b2GPI)-specific immune responses in BALB/c mice. The
overall immune response characteristics, especially its pathogenic potential, depended on adjuvants applied prior and in combination with TTd. Beside structural homology between TTd and b2GPI, tolerance
toward b2GPI could be impaired by adjuvants acting as polyclonal
stimulators. In order to clarify the impact of adjuvants, phenotypic and
functional analyses of immune system cells within spleen were done
upon immunization completion.
Materials and methods: Non- or CFA-pretreated BALB/c mice were
immunized with TTd (3 · 100 lg/dose; 2-week intervals) mixed with
alum or 2.5M glycerol. Ex vivo analyses of CD3, CD4, CD8, CD19, CD
25, CD27 and mIgM expression on age-matched control and
immunized mice’s splenocytes were done by flow cytometry. Changes
in TLR2, TLR4 and TLR9 expression were assessed indirectly, by
measuring cytokine production, following in vitro stimulation of
splenocytes with appropriate agonist.
Results: TTd-immunization diminished CD27 expression on T cells
implying on their differentiation into potent effector cells. T cell
activation (increase in CD25 expression and the raise of percentage of
CD4+ CD8+ CD3+
) and B cell activation (rise in percentage of
CD19+ CD25+ cells and the increase of mIgM density) occurred in all
immunized mice, being more intensive in CFA-pretreated groups.
Irrespective to the applied immunization protocol, statistically significant rise in abundance of CD4- CD8- cells (often cited as cells having
suppressive potential) within T cell pool was registered too. Differences
in cytokines production (IL4, IL10, IFNc) registered upon in vitro
stimulation with peptidoglycan, LPS and CpG ODN implied on
context-dependant modulation of TLR2, TLR4 and TLR9 expression
on splenocytes.
Conclusions: TTd-hyperimmunization promoted concomitant rise in
abundance of activated cells and the cells that have suppressive
potential. This could be regarded as an attempt of the system to retain
control. Imbalance in percentages and activities between activated cells
and those having suppressive potential, highly influenced by the
context of TTd application, is most likely the cause for the observed
pathology appearance after TTd hyperimmunization.",
publisher = "Wiley",
journal = "Immunology (Abstracts of the European Congress of Immunology, 5-8 September 2012, Glasgow, Scotland)",
title = "Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application",
pages = "423-423",
number = "s1",
volume = "137",
url = "https://hdl.handle.net/21.15107/rcub_intor_711"
}

Stojanović, M., Živković, I., Inić-Kanada, A., Petrušić, V., Marinković, E., Stojićević, I.,& Dimitrijević, I.. (2012). Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application. in Immunology (Abstracts of the European Congress of Immunology, 5-8 September 2012, Glasgow, Scotland)
Wiley., 137(s1), 423-423.
https://hdl.handle.net/21.15107/rcub_intor_711

Stojanović M, Živković I, Inić-Kanada A, Petrušić V, Marinković E, Stojićević I, Dimitrijević I. Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application. in Immunology (Abstracts of the European Congress of Immunology, 5-8 September 2012, Glasgow, Scotland). 2012;137(s1):423-423.
https://hdl.handle.net/21.15107/rcub_intor_711 .

Stojanović, M., Živković, Irena, Inić-Kanada, A., Petrušić, V., Marinković, E., Stojićević, I., Dimitrijević, I., "Phenotypic and functional characteristics of splenocytes in tetanus toxoid-hyperimmunized Balb/c mice is influenced by the context of tetanus toxoid application" in Immunology (Abstracts of the European Congress of Immunology, 5-8 September 2012, Glasgow, Scotland), 137, no. s1 (2012):423-423,
https://hdl.handle.net/21.15107/rcub_intor_711 .

TY  - JOUR
AU  - Dimitrijević, Ljiljana
AU  - Stojanović, M.
AU  - Cirić, B.
AU  - Radulović, M.
AU  - Stojanović, R.
AU  - Popović, Zoran
AU  - Inić-Kanada, Aleksandra
AU  - Živković, Irena
PY  - 2004
UR  - http://intor.torlakinstitut.com/handle/123456789/178
AB  - In this paper we report data regarding the IgM Y7 cross-reactive idiotope (CRIo) obtained by analysis of: 1) its V-gene subgroup dependance, 2) the frequency of its expression on human monoclonal IgMs and IgM molecules from normal and pathological sera. Furthermore, comparison of epitopic repertoire and nature of binding of human monoclonal IgMs expressing Y7 CRIo was performed to confirm the natural antibody properties of these molecules. IgM isolated from sera of patient DJ (IgM DJ) which expresses the Y7 idiotope has been classified to V(H)3/V(L)2 subgroup. From ten IgMs tested only IgM from patient RD (IgM RD) has been shown to express Y7 idiotope. Y7(+) human IgMs bound to ssDNA, lactic acid bacteria, mouse laminin, porcine thyroglobulin and mouse IgG. Higher percentage of the expression of Y7 CRIo was detected in the sera of patients suffering from autoimmune diseases such as lupus, rheumatoid arthritis and psoriasis vulgaris as well as in patients suffering from chronic infections of the lower urinary tract. Antigen binding repertoire and properties of Y7(+) monoclonal IgM, frequency of Y7 expression on monoclonal IgMs and its concentration in normal and pathological sera indicate the important biological role of this CRIo within the immune system.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Immunological Investigations
T1  - Expression of Y7 cross-reactive idiotope on human IgM molecules
EP  - 14
IS  - 1
SP  - 1
VL  - 33
DO  - 10.1081/IMM-120027680
ER  - 

@article{
author = "Dimitrijević, Ljiljana and Stojanović, M. and Cirić, B. and Radulović, M. and Stojanović, R. and Popović, Zoran and Inić-Kanada, Aleksandra and Živković, Irena",
year = "2004",
abstract = "In this paper we report data regarding the IgM Y7 cross-reactive idiotope (CRIo) obtained by analysis of: 1) its V-gene subgroup dependance, 2) the frequency of its expression on human monoclonal IgMs and IgM molecules from normal and pathological sera. Furthermore, comparison of epitopic repertoire and nature of binding of human monoclonal IgMs expressing Y7 CRIo was performed to confirm the natural antibody properties of these molecules. IgM isolated from sera of patient DJ (IgM DJ) which expresses the Y7 idiotope has been classified to V(H)3/V(L)2 subgroup. From ten IgMs tested only IgM from patient RD (IgM RD) has been shown to express Y7 idiotope. Y7(+) human IgMs bound to ssDNA, lactic acid bacteria, mouse laminin, porcine thyroglobulin and mouse IgG. Higher percentage of the expression of Y7 CRIo was detected in the sera of patients suffering from autoimmune diseases such as lupus, rheumatoid arthritis and psoriasis vulgaris as well as in patients suffering from chronic infections of the lower urinary tract. Antigen binding repertoire and properties of Y7(+) monoclonal IgM, frequency of Y7 expression on monoclonal IgMs and its concentration in normal and pathological sera indicate the important biological role of this CRIo within the immune system.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Immunological Investigations",
title = "Expression of Y7 cross-reactive idiotope on human IgM molecules",
pages = "14-1",
number = "1",
volume = "33",
doi = "10.1081/IMM-120027680"
}

Dimitrijević, L., Stojanović, M., Cirić, B., Radulović, M., Stojanović, R., Popović, Z., Inić-Kanada, A.,& Živković, I.. (2004). Expression of Y7 cross-reactive idiotope on human IgM molecules. in Immunological Investigations
Taylor & Francis Inc, Philadelphia., 33(1), 1-14.
https://doi.org/10.1081/IMM-120027680

Dimitrijević L, Stojanović M, Cirić B, Radulović M, Stojanović R, Popović Z, Inić-Kanada A, Živković I. Expression of Y7 cross-reactive idiotope on human IgM molecules. in Immunological Investigations. 2004;33(1):1-14.
doi:10.1081/IMM-120027680 .

Dimitrijević, Ljiljana, Stojanović, M., Cirić, B., Radulović, M., Stojanović, R., Popović, Zoran, Inić-Kanada, Aleksandra, Živković, Irena, "Expression of Y7 cross-reactive idiotope on human IgM molecules" in Immunological Investigations, 33, no. 1 (2004):1-14,
https://doi.org/10.1081/IMM-120027680 . .