Human fetuses are able to mount an adultlike CD8 T-cell response

Abstract

Fetal/neonatal immune responses generally are considered to be immature and weaker than that of adults. We have studied the cord-blood T cells of newborns congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas disease. Our data demonstrate a predominant activation of CD8 T cells expressing activation markers and armed to mediate effector functions. The analysis of the T-cell receptor beta chain variable repertoire shows the oligoclonal expansion of these T lymphocytes, indicating that activation was driven by parasite antigens. Indeed, we have detected parasite-specific CD8 T cells secreting interferon-γ after coincubation with live T cruzi. This response is enhanced in the presence of recombinant interleukin-15, which limits the T-cell spontaneous apoptosis. These findings point out that the fetal immune system is more competent than previously appreciated, since fetuses exposed to live pathogens are able to develop an adultlike immune CD8 T-cell response.

Dissecting the defects in the neonatal CD8+ T-cell response

“…110,111 However, more important than decreased absolute numbers of cells, neonatal CD8 + T-cell function is diminished and varies depending on the pathogen and context of infection. 1,110,[112][113][114][115] A longitudinal study of 61 Kenyan infants and 65 infants from New York revealed the age of HIV infection to be a primary outcome determining factors. Infants infected with HIV in utero, peripartum or postpartum has varying magnitude and function of CD8 + T cells strongly dependent on the age of infection, independent of their antiretroviral therapy use.…”

Killer cell immunoglobulin‐like receptor expression induction on neonatal CD8+ T cells in vitro and following congenital infection with Trypanosoma cruzi

“…Human congenital infection with T. cruzi triggers a clonal expansion of activated CD8 + T cells. 21 In this study, we confirmed the activation of CD8 + T cells from congenitally infected newborns with a significant increase of CD45R0 expression (median 21Á6%, range 14Á4-39Á3, n = 10) and significant decrease of CD62 ligand expression (median 74Á9%, range 18Á9-86Á6, n = 9) compared with uninfected newborns (median 7Á3%, range 0Á2-16Á1, n = 13 and median 91%, range 54Á7-96Á3, n = 12, respectively) (P < 0Á05). We also confirmed that cord blood T cells barely expressed iNKRs (CD94/NKG2A, CD158a, CD158b, CD158e, CD158k and CD85j) in healthy newborns (Fig.…”

“…We reported that a strong cord blood CD8 + T-cell response can develop in newborns congenitally infected with Trypanosoma cruzi, the protozoal agent of Chagas' disease. 21 Expansion and differentiation of these mature CD8 + T cells in utero provided us with a unique setting to look for the induction of KIR in vivo following antigen stimulation. In the present study, we found that both in vitro IL-2 stimulation and congenital infection could induce significant expression of KIRs on cord blood CD8 + T cells.…”

Differing activation status and immune effector molecule expression profiles of neonatal and maternal lymphocytes in an African population

“…The dogmatic view that the neonatal immune system has intrinsically less immunological capacity per se than that of adults has recently been challenged by reports suggesting that neonatal cells are naive but nevertheless immunologically competent, that the observed differences are of a quantitative nature and that neonatal cells have the capacity to mount adult-like responses under appropriate conditions of stimulation. [3][4][5] Because immune cells mediate many of their functions by secretion of cytokines, differences in cytokine production capacity help to characterize functional differences in neonatal and adult immune responses. Several studies have compared cytokine production by neonatal and adult cells in non-African populations.…”