Immunological Characteristics between αß TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice / Características imunológicas entre células TDC αß e TDC γδ no baço de camundongos com câncer de mama induzido

Abstract Objective To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer. Methods Thirty female Balb/c mice were divided into 2 groups: control group (n=15) and induced-4T1 group (n=15), in which the mice received 2 x 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17). Results A total of 26.53% of γδ TDC- control group (p<0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p<0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p<0.0001). Conclusion Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

Resumo Objetivo Esclarecer o possível papel antitumoral das células TDC γδ e TDC αβ em um modelo experimental de câncer de mama. Métodos Trinta baços de camundongos Balb/c analisados por citometria de fluxo, separados entre grupo controle (n=15) e o grupo tumoral induzido por 4T1 (n=15). Resultados Presença de 26,53% de TDC γδ nos camundongos do grupo controle (p<0,0001), proporção de TDC αβ menor em células esplênicas do que TDC γδ; no entanto, estes dois tipos de células são reduzidos emcondições tumorais (p<0,0001), e a proporção de citocinas IFN-γ, TNF-α, IL-12 e IL-17 produzidas pelas célula TDC γδ foi maior do que as produzidas pelas células TDC αβ, mas foram diminuídas sob condições de resposta ao sistema imunológico relacionada ao tumor (p<0,0001). Conclusão Camundongos saudáveis induzidos ao tumor de mama 4T1 apresentaram TDC com repertório TCR γδ. Estas células expressam moléculas citotóxicas de linfócitos T, produzindo citocinas proinflamatórias anti-tumor.

Preservation of cytotoxic granule production in response to mycobacterial antigens by T-lymphocytes from vertically HIV-infected Brazilian youth on effective combined antiretroviral therapy

ABSTRACT Background: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. Methods: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. Results: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. Conclusions: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.

Los fectos humanos estan capaces de generar una respuesta inmune T CD8 similar a la de los adultos / The human fetuses are be able to develep an adult-like immune CD8 T-cell response

Fetal/Neonatal immune responses are generally considered to be immature and weaker than in adults. We have sudied the cord blood T-cells of newborns congenitally-infected whith Tripanosoma cruzi, the protozoan agent of Chagas' disease. Our data demonstrate a predominant activation of CD8 T-cells expressing activation markers and armed to mediate effector functions. Indeed, we have detected parasite-specific CD8 T-cells secreting interferon-ã. Such response is enchanced in the presence of rIL-15. These findings point out that the fetal immune system is more competent than previously appreciated, since fetuses exposed to live pathogens are able to develop an adult-like immune CD8 T-cell response.

Receptores de células T y complejo CD3 / T cell receptors and CD3 complex

Tanto las células T como las células B contactan con antígenos a través de moléculas especializadas presentes en su superficie. En las células T, se han descrito dos tipos de estructuras para interactuar con los antígenos, se trata de los TCR alfa-beta y TCR gamma-delta. El primero, es el que se distribuye más ampliamente en las células T periféricas y timocitos portadores de un receptor definido. Se trata de moléculas heterodiméricas compuestas de dos cadenas polipeptídicas unidas entre sí. En una célula se expresan miles de copias de un receptor cuyas especificidades epitópicas son idénticas, sin embargo, la presencia de un tipo de receptor excluye la del otro. Las células T pueden ser, independiente del receptor desplegado, CD8- CD4+ o CD8+ CD4-, cumpliendo, por lo tanto, funciones ayudadoras o citotóxicas, respectivamente. Ambos receptores para efectuar sus actividades requieren de la expresión de un complejo proteico llamado CD3, compuesto por 5 proteínas denominadas alfa, delta, épsilon, dseta y eta cuya misión, en presencia de interacción con el antígeno, es transducir señales a través de la membrana celular del linfocito. El receptor de la célula T reconoce al antígeno asociado a proteínas de la membrana plasmática, conocidas como moléculas de histocompatibilidad clase I o II, dependiendo si se trata de células no inmunológicamente comprometidas, o bien, células presentadoras de antígeno o linfocitos, respectivamente. La estrategia para generar diversidad en los TCR es similar a la utilizada para las inmunoglobulinas. Los genes que codifican para los TCR se generan por medio de recombinaciones somáticas de segmentos génicos durante la etapa germinal de las células T

A maternally-inherited alteration in the T cell repertoire of balb/c mice

Se ha demostrado que los virus exógenos del tumor mamario murino (MMTV) transmitidos por leche, inducen la expresión de diferentes superantígenos en los huéspedes infectados. Cada uno de estos superantígenos es capaz de inducir la deleción clonal progresiva de las células T portadoras de determinados elementos Vß de su receptor (TCR). En este trabajo se describe la existencia de una alteración en el repertorio T de los ratones BALB/c de una colonia. Dicha alteración, transmitida por vía materna, involucra la deleción de las células T CD4+ que expresan las cadenas Vß2 y Vß14 del TCR y correlaciona con una alta incidencia de tumores de mama. Estos resultados indican la transmisión materna de un superantígeno(s), probablemente asociado a la presencia de virus MMTV en la leche