Modeling the specific CD4+ T cell response against a tumor neoantigen.

The antitumor activity of CD4(+) T cells is increasingly acknowledged in both humans and mice. The involved mechanisms have been mostly studied using transplanted tumor mouse systems. In these models, many tumor cells die at the time of implantation leading to the release of Ag in an inflammatory context contrasting with the slow and nondestructive growth of early-stage human tumors. In this study, we show that the presentation of a MHC class II-restricted model Ag (male, DBY) released by dying tumor cells may last more than 4 wk. The duration of Ag presentation varies according to the way the cells are killed before implantation. To avoid this artifactual early priming of the host precluding the study of the interactions between the immune system and tumors at the steady state, we generated a cell line expressing the DBY Ag in an inducible manner. Ag expression can be efficiently induced in vivo several days after tumor implantation. We show that the Ag reaches the lymph node and activates naive CD4(+) T cells to proliferate and recirculate. We did not observe de novo induction of tumor-specific regulatory T cells. However, we observed Th1/Th17 effector cells in the tumor draining lymph node and tumors. Thus, when a neoantigen appears in established tumors, the immune system is not ignorant and naive CD4(+) T cells are not tolerized. This opens up the possibility of therapeutic vaccines improving the immune response toward tumor-specific neoantigens.

C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells.

For decades Experimental Autoimmune Encephalitis (EAE) has remained as an unsurpassed multiple sclerosis (MS) animal model. C-Phycocyanin (C-Pc) has been reported to exhibit pharmacological properties that may be expected to symptomatically improve EAE and MS. However, in this paper we reveal a basic underlying mechanism that may provide a new approach to the rationale of the overall beneficial effect of this natural antioxidant. We demonstrate that C-Pc is able to trigger mechanisms preventing or downgrading EAE expression and induces a regulatory T cell (Treg) response, in peripheral blood mononuclear cells (PBMC) from MS patients. These results agree with reports suggesting that Treg limit acute MS attacks and that C-Pc may act as a neuroprotector and thereby reverts the organic and functional damage in neurodegenerative disorders of the central nervous system (CNS). Moreover, evidence is provided on the antioxidant activity of C-Pc within the CNS, intended to improve the myelin and axonal damage of EAE induced Lewis rats. Our results indicate that specific Treg activation may represent a central and essential mechanism in supporting the therapeutic potential of C-Pc for MS and may lead to new and more effective therapies; this property would then complement and enhance other proven active principles such as interferons (IFN), giving rise to combined therapies.

Rationale for Targeting CD6 as a Treatment for Autoimmune Diseases.

CD6 is a 105-130 kDa surface glycoprotein expressed on the majority of T cells and a subset of B cells. The human cd6 gene maps to chromosome 11, and the expression of its protein product is tightly regulated. CD6 mediates cellular adhesion migration across the endothelial and epithelial cells. In addition, it participates in the antigen presentation by B cells and the subsequent proliferation of T cells. CD6 may bind in trans to surface glycoproteins (such as ALCAM and 3A11), or to microbial lipopolysaccharides, and may bind in cis to endogenous ligands (such as CD3 and CD5), and thereby deliver a costimulatory signal. Transinteractions are reinforced during autoimmune diseases (e.g., rheumatoid arthritis (RA), Sjögren's syndrome, and multiple sclerosis) and some cancers. Based on experimental data and on clinical results in RA and psoriasis, we believe that the recent humanized anti-CD6-specific mAb T1h may act as a regulator of the immunological response in addition to its function as an anti-T- and -B cell agent.

Autoreactive B cells and epigenetics.

Autoreactive B cells are central in the pathogenesis of autoimmune diseases (AID) not only by producing autoantibodies but also by secreting cytokines and by presenting autoantigens. Changes in DNA methylation, histone modifications, and miRNA expression, the hallmarks of epigenetic failure, characterize B cells isolated from patients with AID, highlighting the contribution of epigenetic processes to autoreactivity. Additional evidence of epigenetic involvement in the development of B cell autoreactivity comes from in vivo and in vitro studies using DNA demethylating agents as accelerating factors or histone deacetylase inhibitors as repressing factors. As a result, a better understanding of the altered epigenetic processes in AID and in particular in B cells opens perspectives for the development of new therapeutics.

Expresión fenotípica de las moléculas CD5 y CD6 en la leucemia linfoide crónica B-CD5+ / The B-CD5+ chronic lymphoid leukemia related to the phenotype expression

Las moléculas CD5 y CD6 tienen función coestimuladora y muestran homología en su estructura. Se evaluó la expresión de la molécula CD6 mediante el uso del anticuerpo monoclonal anti-CD6 (T1) en el inmunofenotipaje celular de pacientes con leucemia linfoide crónica By se comparó con la expresión de la molécula CD5.Los resultados demuestranuna homología en la expresión fenotípica de ambas moléculas, CD5 y CD6, lo que asociado con que ambos receptores linfocitarios se encuentran físicamente vinculados, permite sugerir que la molécula CD6 constituye un marcador biológico de interés en la evaluación del pronóstico y la posibilidad de nuevas variantes terapéuticas en esta enfermedad.

CD5 and CD6 molecules have a co-stimulant function and show homology in structure. We assessed CD6 molecule expression using anti-CD6 (T1) monoclonal antibody in the cellular immunophenotyping from patients presenting B chronic lymphoid leukemia, and it was compared to CD5 molecule expression. Results show a homology in phenotype expression of both molecules (CD5 and CD6), what associated with the fact that both lymphocyte receptors are physically linked, allow to suggest that CD6 molecule is a interesting biological marker in prognosis assessment, and the possibility of new therapeutic variants in this disease.

Expresión fenotípica de las moléculas CD5 y CD6 en la leucemia linfoide crónica B-CD5+ / The B-CD5+ chronic lymphoid leukemia related to the phenotype expression

Las moléculas CD5 y CD6 tienen función coestimuladora y muestran homología en su estructura. Se evaluó la expresión de la molécula CD6 mediante el uso del anticuerpo monoclonal anti-CD6 (T1) en el inmunofenotipaje celular de pacientes con leucemia linfoide crónica By se comparó con la expresión de la molécula CD5.Los resultados demuestranuna homología en la expresión fenotípica de ambas moléculas, CD5 y CD6, lo que asociado con que ambos receptores linfocitarios se encuentran físicamente vinculados, permite sugerir que la molécula CD6 constituye un marcador biológico de interés en la evaluación del pronóstico y la posibilidad de nuevas variantes terapéuticas en esta enfermedad(AU)

CD5 and CD6 molecules have a co-stimulant function and show homology in structure. We assessed CD6 molecule expression using anti-CD6 (T1) monoclonal antibody in the cellular immunophenotyping from patients presenting B chronic lymphoid leukemia, and it was compared to CD5 molecule expression. Results show a homology in phenotype expression of both molecules (CD5 and CD6), what associated with the fact that both lymphocyte receptors are physically linked, allow to suggest that CD6 molecule is a interesting biological marker in prognosis assessment, and the possibility of new therapeutic variants in this disease(AU)

Aplicación de la citometría de flujo en el diagnóstico inmunológico de los linfomas cutáneos T / Application of flow cytometry in the immunological diagnosis of cutaneous T-cell lymphomas

Se comunican las características inmunofenotípicas de 7 pacientes (5 del sexo masculino y 2 del femenino) con el diagnóstico clínico-morfológico de linfomas cutáneos de células T, atendidos en la consulta de Hematología del Instituto de Hematología e Inmunología. La edad de los pacientes osciló entre 17 y 88 años. El inmunodiagnóstico se realizó por inmunofluorescencia directa con un panel de anticuerpos monoclonales que incluyó marcadores linfoides B y T: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 y CD25. La lectura se realizó en un clitómetro de flujo FaCScan (Becton-Dickinson ). Cada marcador se consideró positivo si un porcentaje mayor al 20 por ciento de los linfocitos expresaba el antígeno. Nuestros resultados mostraron que en la mayoría de los pacientes predominó el patrón general de los linfocitos T con función auxiliadora (CD3+, CD4+, CD8-). Se corrobora que la citometría de flujo es un procedimiento más rápido y menos laborioso que otros métodos de inmunofenotipaje celular, que nos permite un diagnóstico de certeza y la aplicación de una terapia efectiva.

The immunophenotypic characteristics of 7 patients (5 males and 2 females) with clinicomorphological diagnosis of cutaneous T-cell lymphomas that received attention at the Hematology Department of the Institute of Hematology and Immunology were reported. The age ot the patients ranged from 17 to 88 years old. The immunodiagnosis was obtained by direct immunofluorescence with a panel of monoclonal antibodies that included B and T lymphoid markers: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 and CD25. The reading was made in a FaCScan flow cytometer (Becton-Dickinson). Each marker was considered positive if a percentage over 20 percent of the lymphocytes expressed the antigen. Our results showed the predominance in most of the patients of a general pattern of T-lymphocytes with auxiliary function (CD3+, CD4+, CD8-). It was corroborated that flow cytometry was a faster and less laborious method than other cellular immunophenotyping methods, and that it allowed to have an accurate diagnosis and to apply an effective therapy.

Aplicación de la citometría de flujo en el diagnóstico inmunológico de los linfomas cutáneos T / Application of flow cytometry in the immunological diagnosis of cutaneous T-cell lymphomas

Se comunican las características inmunofenotípicas de 7 pacientes (5 del sexo masculino y 2 del femenino) con el diagnóstico clínico-morfológico de linfomas cutáneos de células T, atendidos en la consulta de Hematología del Instituto de Hematología e Inmunología. La edad de los pacientes osciló entre 17 y 88 años. El inmunodiagnóstico se realizó por inmunofluorescencia directa con un panel de anticuerpos monoclonales que incluyó marcadores linfoides B y T: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 y CD25. La lectura se realizó en un clitómetro de flujo FaCScan (Becton-Dickinson ). Cada marcador se consideró positivo si un porcentaje mayor al 20 por ciento de los linfocitos expresaba el antígeno. Nuestros resultados mostraron que en la mayoría de los pacientes predominó el patrón general de los linfocitos T con función auxiliadora (CD3+, CD4+, CD8-). Se corrobora que la citometría de flujo es un procedimiento más rápido y menos laborioso que otros métodos de inmunofenotipaje celular, que nos permite un diagnóstico de certeza y la aplicación de una terapia efectiva(AU)

The immunophenotypic characteristics of 7 patients (5 males and 2 females) with clinicomorphological diagnosis of cutaneous T-cell lymphomas that received attention at the Hematology Department of the Institute of Hematology and Immunology were reported. The age ot the patients ranged from 17 to 88 years old. The immunodiagnosis was obtained by direct immunofluorescence with a panel of monoclonal antibodies that included B and T lymphoid markers: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 and CD25. The reading was made in a FaCScan flow cytometer (Becton-Dickinson). Each marker was considered positive if a percentage over 20 percent of the lymphocytes expressed the antigen. Our results showed the predominance in most of the patients of a general pattern of T-lymphocytes with auxiliary function (CD3+, CD4+, CD8-). It was corroborated that flow cytometry was a faster and less laborious method than other cellular immunophenotyping methods, and that it allowed to have an accurate diagnosis and to apply an effective therapy(AU)

Aplicación de la citometría de flujo en el diagnóstico inmunológico de los linfomas cutáneos T / Application of flow cytometry in the immunological diagnosis of cutaneous T-cell lymphomas

Se comunican las características inmunofenotípicas de 7 pacientes (5 del sexo masculino y 2 del femenino) con el diagnóstico clínico-morfológico de linfomas cutáneos de células T, atendidos en la consulta de Hematología del Instituto de Hematología e Inmunología. La edad de los pacientes osciló entre 17 y 88 años. El inmunodiagnóstico se realizó por inmunofluorescencia directa, con un panel de anticuerpos monoclonales que incluyó marcadores linfoides B y T: CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD22 y CD25. La lectura se realizó en un clitómetro de flujo FaCScan (Becton-Dickinson). Cada marcador se consideró positivo si un porcentaje mayor al 20 % de los linfocitos expresaba el antígeno. Nuestros resultados mostraron que en la mayoría de los pacientes predominó el patrón general de los linfocitos T con función auxiliadora (CD3+, CD4+, CD8-). Se corrobora que la citometría de flujo es un procedimiento más rápido y menos laborioso que otros métodos de inmunofenotipaje celular, que nos permite un diagnóstico de certeza y la aplicación de una terapia efectiva.

The immunophenotypic characteristics of 7 patients (5 males and 2 females) with the clinical-morphological diagnosis of cutaneous T-cell lymphoma that received attention at the Hematology service of the Institute of Hematology and Immunology were reported. The patients were between 17 and 88 years old. The immunodiagnosis was made by direct immunofluorescence with a panel of monoclonal antibodies that included B and T lymphoid markers: CD2, CD3, CD4; CD5, CCD7, CD8, CD19, CD22 and CD25. The reading was obtained in a FaCScan (Becton-Dickinson) flow cytometer. Every marker was considered positive if a percentage over 20 % expressed the antigen. Our results showed the prevalence of the general pattern of T lymphocytes with auxiliary function (CD3+, CD4+, CD8-). It was proved that flow cytometry is a faster and less laborious than other methods of cellular phenotyping, allowing an accurate diagnosis and the application of an effective therapy.