Circulating rotavirus-specific T cells have a poor functional profile

Abstract

Frequencies of circulating T cells producing IFN-γ, TNF-α, and IL-2, and percentages of T cells proliferating after stimulation with rotavirus (RV), tetanus toxoid, and influenza were evaluated in PBMC derived from healthy adults and children. In addition, the potential anergic state of RV-specific T cells was analyzed by stimulation of PBMC with RV antigen in the presence of three anergy inhibitors (rIL-2, rIL-12, or DGKα-i). The quality and magnitude of RV-T cell responses were significantly lower than those of tetanus toxoid and influenza antigens. RV-CD4 T cell response was enriched in monofunctional IFN-γ(+) cells, while influenza-CD4 and tetanus toxoid-CD4 T cell responses were enriched in multifunctional T cells. Moreover, rIL-2--unlike rIL-12 or DGKα-i--increased the frequencies of RV-CD4 TNF-α(+), CD4 IFN-γ(+), and CD8 IFN-γ(+) cells. Thus, circulating RV-T cells seem to have a relatively poor functional profile that may be partially reversed in vitro by the addition of rIL-2.

Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa

“…Assuming that ART is started shortly after birth in HIV+ infants, as in this study, the third dose will be given after a long period of ART. This might influence persistence, as suggested by a report that a third dose of RV1, compared to the recommended two doses for that vaccine, resulted in higher serum IgA titers and significantly greater efficacy in the second year post-vaccination in a developing world setting [51]. …”

Rotavirus infection

“…A similar situation might exist in young children in whom intestinal IgA antibodies wane 90 and rotavirus-specific CD4 + T cells are found at very low levels. Indeed, children with acute rotavirus gastroenteritis have very low levels of rotavirus-specific CD4 + T cells, which almost exclusively produce IFNγ 91,97 . Considering the poor ability of children to develop rotavirus neutralizing antibodies and that protection against rotavirus reinfection is age-dependent, the low levels of rotavirus-specific CD4 + T cells in younger children might be a key factor in protection from severe recurrent illness and in the response to rotavirus vaccination 98 .…”

“…When compared directly to influenza virus CD4 + T cell responses or tetanus toxin CD4 + T cell responses, the frequencies of rotavirus-specific CD4 + T cells in healthy adults have been shown to be low 97 but similar to levels of CD4 + T cells specific for other mucosal respiratory viruses 91 . Interestingly, in adults, rotavirus-specific CD4 + T cells have a terminal effector memory cellular phenotype, suggesting that they do not provide long-term immunity 97 . Collectively, these data suggest that in adults, the systemic CD4 + T cell response to rotavirus infection is poor, which might explain the absence of sterilizing immunity and the presence of moderately frequent, mild recurrent infections.…”

Papel del TGF-β en la inmunidad contra los rotavirus

“…A pesar de que demostramos que los niños tenían frecuencias esperadas de LTreg, no detectamos en sus células el mismo efecto que en los adultos (Mesa, et al, 2010). De acuerdo con estos resultados, muy recientemente mostramos que en adultos sanos, en comparación con LT CD4 específicos de toxoide tetánico y del virus de la influenza, LTCD4-RV parecen proliferar menos y estar enriquecidos en aquellos que sólo producen IFN-γ (Parra, et al, 2014b). Esto está de acuerdo con un estudio complementario en que se mostró, con tetrameros de clase II, que los LT CD4 específicos de rotavirus expresan marcadores de migración intestinal y, por lo tanto, muy probablemente fueron estimulados en el intestino (Parra, et al, 2014a).…”