Humoral and cellular immune response of mice challenged with Yersinia pestis antigenic preparations

ABSTRACT Objectives: The plague, which is an infectious disease caused by Yersinia pestis, still threatens many populations in several countries. The worldwide increase in human plague cases and the potential use of the bacteria as a biological weapon reinforce the need to study the immunity that is induced by potential vaccine candidates. To determine the immunogenicity of antigenic preparations based on the F1 protein and the total extract from Y. pestis, we assessed the role of these antigens in inducing an immune response. Methods: The immunogenicity of antigenic preparations based on the Y. pestis (YP) total extract and the Y. pestis fraction 1 capsular antigen protein (F1) was determined in Swiss-Webster mice immunized with 40 µg or 20 µg for each preparation. Immunophenotyping was performed by flow cytometry. Results: Animals immunized with the YP total extract did not elicit detectable anti-F1 antibodies (Ab) in the hemaglutination/inhibition (HA/HI) test. Animals immunized with 40 µg or 20 µg of the F1 protein produced anti-F1 Abs, with titres ranging from 1/16 to 1/8132. The average of CD3+-CD4+ and CD3+-CD8+ T cells did not differ significantly between the groups. Neither YP total extract nor F1 protein induced a significant expression of IFN-γ and IL-10 in CD4+ T lymphocytes. In addition, F1 failed to induce IFN-γ expression in CD8+ T cells, unlike the YP total extract. Conclusion: The results showed that F1 protein is not an immunogenic T cell antigen, although the YP total extract (40 µg dose) favoured CD8+ T cell-mediated cellular immunity.

Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients / Níveis plasmáticos de creatinina e citocinas relacionados com compatibilidade HLA em pacientes transplantados renais

ABSTRACTIntroduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA) typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG).Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3) was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively). The median plasma levels of cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α) were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

RESUMOIntrodução:O sucesso de um transplante renal depende da prevenção da rejeição ao órgão por parte do sistema imune do receptor ao reconhecer aloantígenos presentes no tecido transplantado. A tipagem de antígenos leucocitários humanos (HLA) é um dos testes empregados no pré-transplante renal e constitui um dos fatores mais importantes para o transplante bem-sucedido.Objetivo:O estudo em questão avaliou os níveis plasmáticos de creatinina e citocinas em pacientes transplantados renais em função da tipagem HLA realizada no período pré-transplante.Métodos:Foram avaliados 40 pacientes transplantados renais de dois centros de transplantes em Belo Horizonte (MG).Resultados:Os pacientes foram distribuídos em grupos de acordo com o número de compatibilidades HLA e constatou-se, por meio de análises estatísticas, que o grupo com mais de três compatibilidades (H3) apresentou níveis significativamente menores de creatinina pós-transplante em relação aos grupos com três ou menos compatibilidades (H2 e H1, respectivamente). As medianas dos níveis plasmáticos das citocinas interleucina 6 (IL-6), fator de necrose tumoral alfa (TNF-α) e interleucina 10 (IL-10) também foram avaliadas em função do número de compatibilidades. Observou-se que as citocinas pró-inflamatórias (IL-6 e TNF-α) estavam significativamente maiores nos grupos com menor compatibilidade HLA. Por outro lado, a citocina reguladora IL-10 apresentou níveis plasmáticos significativamente maiores no grupo com mais compatibilidades entre doador e receptor.Conclusão:Esses achados permitem inferir que a tipagem HLA de doadores e receptores pré-transplante pode influenciar na função renal do enxerto pós-transplante, bem como contribuir para o desenvolvimento e a escolha de novas estratégias de tratamento.