Effects of interleukin-12 and interleukin-15 on measles-specific T-cell responses in vaccinated infants

Abstract

Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-gamma release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-gamma release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L(+) T cells expressed IFN-gamma. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines.

FIG. 1.

T-cell proliferation in infants after measles immunization compared with vaccinated adults. Shown are the mean counts per minute (cpm) and standard error (SE) from measles-stimulated PBMCs in infants (solid bars) after measles immunization (ME), and vaccinated adults (hatched bars) in the presence and absence of human recombinant interleukin-12 or interleukin-15 or both. Reported cpm were calculated as cpm in antigen-stimulated wells minus the cpm in control wells. Blood samples were collected 12 or 24 wk after measles immunization in infants who were 6, 9, or 12 mo of age at the time of immunization and in adults aged 20–49 y.

FIG. 2.

Mean IFN-γ concentration from stimulated PBMCs in infants after measles immunization compared with vaccinated children and adults. Shown is the mean IFN-γ concentration (pg/mL) and standard error (SE) released from measles-stimulated PBMCs in infants (solid bars) after measles immunization (ME), and in vaccinated children (striped bars) and adults (dotted bars) in the presence and absence of rhIL-12 or rhIL-15 or both. Infants were 6, 9, or 12 mo of age at the time of immunization, and samples were collected 12–24 wk after immunization.

FIG. 3.

Flow cytometric analysis of measles-specific CD4⁺ T-cell responses in vaccinated infants compared with adults. (A) Shown are representative results of measles-specific CD4⁺ T cells that express CD40-L (right and left top panels) and IFN-γ (right top and bottom panels) from a 9-mo-old infant (left histogram) and an adult (right histogram). The numbers in each histogram represent the percentage of measles-specific CD4+CD40-L+ T cells that also express IFN-γ (top right panel) from 50,000 CD4⁺ T cells. The infant was immunized with Attenuvax at 9 mo of age and a blood sample collected 12 wk after immunization. (B) Shown are the individual percentages and mean percentage of measles-specific CD4⁺ T cells that express CD40-L (left panel) and both CD40-L and IFN-γ (right panel) in infants vaccinated with measles at 6 (circles), 9 (triangles), 12 (diamonds) months of age, and vaccinated adults (squares). Infants were 6, 9, or 12 mo of age at the time of immunization, and samples were collected 12–24 wk after immunization.