T-cell subpopulations αβ and γδ in cord blood of very preterm infants : The influence of intrauterine infection

Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPreterm infants are very susceptible to infections. Immune response mechanisms in this group of patients and factors that influence cord blood mononuclear cell populations remain poorly understood and are considered insufficient. However, competent immune functions of the cord blood mononuclear cells are also described. The aim of this work was to evaluate the T-cell population (CD3+) with its subpopulations bearing T-cell receptor (TCR) αβ or TCR γδ in the cord blood of preterm infants born before 32 weeks of gestation by mothers with or without an intrauterine infection. Being a pilot study, it also aimed at feasibility check and assessment of an expected effect size. The cord blood samples of 46 infants age were subjected to direct immunofluorescent staining with monoclonal antibodies and then analyzed by flow cytometry. The percentage of CD3+ cells in neonates born by mothers with diagnosis of intrauterine infection was significantly lower than in neonates born by mothers without infection (p = 0.005; Mann-Whitney U test). The number of cells did not differ between groups. Infection present in the mother did not have an influence on the TCR αβ or TCR γδ subpopulations. Our study contributes to a better understanding of preterm infants' immune mechanisms, and sets the stage for further investigations.Peer reviewedFinal Published versio

The protective role of T-cell receptor Vγ1+ T cells in primary infection with Listeria monocytogenes

We have previously reported that the T-cell receptor (TCR) γδ+ T cells increase in mice infected with an intracellular bacteria Listeria monocytogenes, and the cells predominantly express Vδ6 and Vγ1 genes. In this study, we used a monoclonal antibody (mAb) specific to TCR Vγ1 to estimate the frequency of Vγ1+ T cells and we discuss their significance in protection against L. monocytogenes. The spleen, liver and peritoneal exudate cells from mice intraperitoneally infected with L. monocytogenes were analysed by flow cytometry. In all the organs investigated, Vγ1+ cells increased predominantly among TCR γδ+ T cells at an early phase (day 5–7) of the infection. To elucidate the significance of the Vγ1+ T cells in the protection against L. monocytogenes, mice were depleted of TCR Vγ1+γδ T cells or all TCR γδ+ T cells by intraperitoneal inoculation of anti-Vγ1 mAb or anti-pan TCR γδ mAb, respectively, before infection with L. monocytogenes. The bacterial growth in the spleen and the liver examined on day 5 after the infection increased significantly by the depletion of TCR Vγ1+ T cells. The numbers of L. monocytogenes in TCR Vγ1+ T-cell-depleted mice were nearly the same as in mice depleted of all TCR γδ+ T cells. These results demonstrated that Vγ1+ T cells are the predominant population of γδ T cells in protection against L. monocytogenes at the early phase of the primary infection

Activation of human Vγ9Vδ2 T cells by a Brucella suis non-peptidic fraction impairs bacterial intracellular multiplication in monocytic infected cells

Human γδ T cells are considered to play an important role in the early response to infection with intracellular pathogens. Evidence has been presented that the percentage of γδ T cells with Vc9Vd2 phenotype is dramatically increased in the peripheral blood of patients with acute brucellosis. This specific γδ T-cell subpopulation is known to be activated by small non-peptidic molecules that can either be produced by the pathogen itself or released from damaged cells after infection. In the present work we provide evidence that Vγ9Vδ2 T lymphocytes from peripheral blood mononuclear cells of healthy donors can be specifically activated by non-peptidic low-molecular-weight compound(s) from Brucella suis lysate. Moreover, we show that Vγ9Vδ2 T cells activated by this B. suis fraction produce tumour necrosis factor-α and interferon-γ, which reduce bacterial multiplication inside infected cells

Recognition of nonpeptide antigens by human Vγ9Vδ2 T cells requires contact with cells of human origin

It is becoming apparent that γδ T cells form an important part of the adaptive immune response. However, the ligands recognized by γδ T cell receptors (TCRs) and the exact biological function of the cells that express this receptor remain unclear. Numerous studies have shown that the dominant human peripheral blood subset of γδ T cells, which express a Vγ9Vδ2 TCR, can activate in response to low molecular weight nonpeptidic molecules. Some of these components have been purified from bacteria or parasites. We examined the activation of polyclonal γδ T cell lines, clones with Vγ9Vδ2 and Vγ9Vδ1 TCRs, and γδ T cells directly ex vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP) antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). Vγ9Vδ2 T cells were able to respond to multiple small organic molecules of highly variable structure whereas cells expressing a similar Vγ9 chain paired with a Vδ1 chain failed to recognize these antigens. Thus, the TCR δ chain appears to make an important contribution to the recognition of these antigens. The kinetics of responses to alkylphosphate and alkylamine antigens differ from those of responses to the nBP pamidronate. These different classes of antigen are believed to have differed mechanisms of action. Such differences explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still retain their ability to activate γδ T cells while alkylphosphate and alkylamine antigens cannot. We also demonstrate that a substantial proportion of the cells that produce IFNγ directly ex vivo in response to PPD are γδ T cells and that γδ T cell activation requires contact with cells of human origin