Rotavirus-specific T-cell responses in young prospectively followed-up children

Abstract

SUMMARYRotavirus is a major cause of gastroenteritis in young children. Antibodies seem to protect against rotavirus infection but cell-mediated immune responses are probably also important for protection. We evaluated the development of T-cell responses to rotavirus in follow-up samples from 20 healthy children with an increased genetic risk for type 1 diabetes. Blood samples from 16 healthy adults were also available for the study. T-cell proliferation was analysed at 3-6 month intervals from the age of 3 months to the age of 4-5 years using the Wa strain of human rotavirus and the NCDV strain of bovine rotavirus as antigens. IgG and IgA antibodies to rotavirus were studied from simultaneously drawn plasma samples with EIA method using NCDV as an antigen. A total of 24 infections were revealed by antibody analysis. Sixteen children showed diagnostic increases in both IgG and IgA antibodies to rotavirus, while 5 children showed increases in IgA antibodies only and 3 in IgG only. Antibody rises were accompanied by T-cell responses to rotavirus (SI > 3) in 9 of the 24 cases. T-cell responses to purified or lysed human rotavirus were stronger after a rise in rotavirus antibodies than the responses before infection ( P = 0·017 and 0·027, respectively). There was a correlation between Tcell responses to purified and lysed human rotavirus and NCDV. Strong T-cell responses to rotavirus were transient and the ability to respond usually disappeared in one year, but in all adults T-cell responses to rotavirus were strong implicating that several infections are needed to develop consistent, strong T-cell responsiveness.

Rotavirus-specific T cell responses and cytokine mRNA expression in children with diabetes-associated autoantibodies and type 1 diabetes

“…Rotavirus infections are documented to induce rotavirus‐specific T cell and cytokine responses in children [8–11], although in our previous follow‐up study T cell responses in young children declined shortly after infection. Persistent responsiveness to rotavirus measured as lymphocyte proliferation was observed in adults [11]. We have now extended our T cell proliferation studies to evaluate further the possible connection between rotavirus and T1D and analysed T cell responsiveness to rotavirus in children with T1D or T1D‐associated autoantibodies.…”

“…Negative control antigens were prepared identically from uninfected MA104 and LLC cells. Human rotavirus [11] and coxsackie B4 virus [14] were purified with sucrose gradient centrifugation. Purified human rotavirus (PRV) and purified coxsackie B4 virus (PCB), human rotavirus lysate (RV) and uninfected MA104 cell lysate were used at 1 µg/ml concentration and NCDV, coxsackie B4 virus lysate (CBV) and uninfected LLC cell lysate at 10 µg/ml concentration.…”

Re–evaluation of the cost–effectiveness and effects of childhood rotavirus vaccination in Norway

“…Direct vaccine–induced protection may be longer, as suggested by other studies [ 23 , 24 ]. The duration of natural immunity was assumed to be on average, one year, but this value is in line with the literature [ 15 , 20 – 22 ]. The potential economic benefits resulting from herd protection among persons above five years of age [ 44 ] were not included in this model, and we may therefore have underestimated the benefits of vaccination.…”

“…Infections were classified as mild, severe or asymptomatic in accordance with Velázquez et al [ 19 ], and the duration of immunity following natural infection was assumed to be one year[ 15 , 20 – 22 ]. The susceptibility and infectivity was assumed to be reduced during the second and later infections relative to the first infection [ 19 ], ( Table 1 ).…”

Development of Cytomegalovirus and Adenovirus-Specific Memory CD4 T-Cell Functions From Birth to Adulthood

“…CD4 ϩ immunity toward acute infections such as rotavirus (10), Respiratory-Syncytial (11), Varicella-Zoster (12), or Influenza virus (13) have more occasionally been investigated, and cellular immunity to adenovirus (AdV) has only been analyzed in transplanted children who could not reflect physiological conditions. Finally, no study has analyzed comparatively memory T-cell development with aging in an acute and a persistent infection.…”