Effects of antenatal and postnatal environments on CD4 T-cell responses to Mycobacterium bovis BCG in healthy infants in the Gambia

Abstract

The Mycobacterium bovis BCG vaccine has a poor record of efficacy in low-income tropical settings. Against this background, we evaluated the immune response of infants to mycobacterial antigens over the 2 years following BCG vaccination at birth by measuring the gamma interferon (IFN-gamma), interleukin-2 (IL-2), and CD154 responses of CD4 T cells. Similar numbers of cells expressed IFN-gamma in infants, 4- to 5-year-old children, and adults, while CD154 was not expressed at comparable levels until the second year of infancy. The IL-2 response remained relatively low in infants, children, and adults but correlated negatively with mother's body mass index and was highest among infants born to Mandinka mothers. Similarly, infants born in the wet season had a stronger CD154 response than those born in the dry season throughout the 2 years of the study. We conclude that the prenatal and perinatal environments have a lasting effect on the response of infants to the BCG vaccine.

FIG. 1.

Gating strategy used to define responding cells. Following gating on lymphocytes expressing high levels of CD4, cross-hairs were set on NHDF-stimulated cells (A) and applied to PPD-stimulated cells (B). The representative sample is from a 12-month-old infant in whom the relatively low percentage of IL-2-producing cells and tendency for coexpression of IFN-γ and CD154 are evident. Percentages refer to events in the labeled quadrant.

FIG. 2.

Fitted lines indicating the relationship between the mother's BMI and the infant IL-2 response following Fisher-Yates transformation at 3 months (A), 6 months (B), 12 months (C), and 2 years (D) of age. The relationship is significant at a P value of 0.035 by GEE.

FIG. 3.

Plots of specific IL-2 responses and specific IFN-γ and IL-2 bifunctional responses of infants of different ethnic groups following Fisher-Yates transformation at 3 months (A), 6 months (B), 12 months (C), and 2 years (D) of age. Significances are derived from a GEE that incorporated all ages.

FIG. 4.

(A) Plots of specific CD154 response following Fisher-Yates transformation measured at 3 months (black circles), 6 months (gray circles), 12 months (black squares), and 2 years (gray squares) of age against date of birth. (B) Summary for each sample time. Significances are derived from comparison between wet and dry seasons by GEE, incorporating data from all ages.