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Effects of interleukin-12 and interleukin-15 on measles-specific T-cell responses in vaccinated infants
Hayley A Gans1, Linda L Yasukawa, Cathryn Z Zhang
1Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA. hagans@stanford.edu
Insights
Infant measles vaccination elicits weaker T-cell responses due to lower cytokine levels. Supplementing with interleukin-12 (IL-12) and interleukin-15 (IL-15) boosts these crucial immune responses in infants.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Infants face higher measles mortality, necessitating effective early protection.
- Measles vaccination in infants yields lower T-cell and B-cell responses compared to adults.
Purpose of the Study:
- Investigate age-related differences in infant immune responses to measles vaccination.
- Determine the impact of recombinant human interleukin-12 (rhIL-12) and interleukin-15 (rhIL-15) on infant immune responses.
Main Methods:
- Compared measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production in infant PBMCs versus children and adults.
- Assessed the effects of rhIL-12 and rhIL-15 on these infant immune responses in vitro.
Main Results:
- Infant peripheral blood mononuclear cells (PBMCs) showed significantly lower T-cell proliferation and IFN-gamma release compared to older individuals.
- Addition of rhIL-12 and rhIL-15 to infant PBMC cultures normalized T-cell proliferation and IFN-gamma release to adult levels.
- Measles antigen stimulation with rhIL-12 and rhIL-15 significantly increased T-cell proliferation and IFN-gamma release in infants.
Conclusions:
- Diminished levels of key cytokines, such as IL-12 and IL-15, may underlie the weaker measles-specific T-cell immunity observed in infants.
- rhIL-12 and rhIL-15 hold potential for enhancing infant immune responses to measles vaccination.
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.
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