IL-12, IFN-γ, and T Cell Proliferation to Measles in Immunized Infants

Author:

Gans Hayley A.1,Maldonado Yvonne1,Yasukawa Linda L.1,Beeler Judy2,Audet Susette2,Rinki Mary M.1,DeHovitz Ross3,Arvin Ann M.1

Affiliation:

1. *Infectious Diseases Division, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305;

2. †Department of Health and Human Services, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20867; and

3. ‡Department of Pediatrics, Palo Alto Medical Foundation, Palo Alto, CA 94301

Abstract

Abstract Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-γ. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-γ, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-γ release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-γ concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-γ production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-γ than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-γ production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-γ and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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