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Link to original content: http://www.ncbi.nlm.nih.gov/pubmed/15196259
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. 2004 Jul;137(1):173-8.
doi: 10.1111/j.1365-2249.2004.02509.x.

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

M Mäkelä  1 , J Marttila, O Simell, J Ilonen
Affiliations

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

M Mäkelä et al. Clin Exp Immunol. 2004 Jul.

Abstract

Rotavirus 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 T-cell 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.

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Figures

Fig. 1
Fig. 1
T-cell responses to different rotavirus antigens. Nebraska calf diarrhoea virus (NCDV), human Wa rotavirus lysate (RV) (a) and purified human Wa rotavirus (PRV)(b). T-cell responses to human Wa rotavirus lysate (P < 0·0001, rs = 0·52, Spearman correlation test) and purified Wa rotavirus (P < 0·0001, rs = 0·56) correlated with responses to bovine NCD virus (number of samples analysed in all three assays = 193) although the responses to human rotavirus were stronger than to bovine rotavirus.
Fig. 2
Fig. 2
T-cell responses to rotavirus lysate before and after serologically demonstrated (a) primary or (b) secondary rotavirus infections. T-cell responses to rotavirus lysate were stronger after an increase in rotavirus antibodies than before the antibody increase, but only a part of infections were associated with a T-cell response to rotavirus.
Fig. 3
Fig. 3
Serological and cellular responses to rotavirus in three children. (a, b) This child had concomitant rises in rotavirus IgG and IgA antibodies and he also showed a cellular response to rotavirus antigens between the ages of 15–18 months. (c, d) This child had maternal IgG and a rise in IgA antibodies at the age of 6 months without an associated cellular response. However, a rise in rotavirus antibodies at the age of 27 months was accompanied by a cellular response to rotavirus. (e, f) IgG antibody titres increased in this child at the age of 12 months and remained elevated thereafter. Cellular responses suggested that the child had experienced several rotavirus infections, at the ages of 12, 18–21 and 48 months. (a, c, e) Rotavirus ○ IgG, • IgA; (b, d, f) ○ NCDV, • RV, □ PRV4, ▪ PPD.
Fig. 4
Fig. 4
T-cell responses to rotavirus antigens. (a) Nebraska calf diarrhoea virus (NCDV), (b) human rotavirus lysate (RV), (c) purified human rotavirus (PRV) and (d) positive control antigen PPD in different age groups of children (3–6 months of age, n = 23; 9–12, n = 26; 15–24, n = 65; 27–36, n = 38; 39–48, n = 31; 51–60, n = 11) and in control adults (n = 16). Median value in each group is shown with the horizontal line in the box. The boxes delineate values between the 25th and 75th percentiles, while values shown with the open circles are values outside this range. T-cell responses to rotavirus were in general weak in the children, while the adult control subjects had stronger T-cell responses to NCDV (P = 0·0001–0·0067, Mann–Whitney U-test), human rotavirus lysate (P = 0·0008–0·011) and purified human rotavirus (P = 0·0044–0·083) than any age group of children. The tendency of weaker proliferation responses in the age group of 51–60 months is probably due to the small sample size in this age group. T-cell responses to PPD were strong also in children.
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