Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1

Bunders, Madeleine J.; Loos, Chris M. van der; Klarenbeek, Paul L.; Hamme, John L. van; Boer, Kees; Wilde, Jim C. H.; Vries, Niek de; Lier, R. A. W. Van; Kootstra, Neeltje A.; Pals, Steven T.; Kuijpers, Taco W.

doi:10.1182/blood-2012-06-437566

Cited by 77 publications

(69 citation statements)

References 38 publications

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“…Therefore, peripheral blood T cells (5–10×10 9 in human blood) represent only 2–2.5% of the total T cell complement in the body 19 , and memory T cells represent the predominant T cell subset in mucosal sites, skin, spleen and bone marrow 20 . Early in infancy, T cells are observed to populate the intestines 21 , and lungs 22 , with 20% of these cells in the intestines exhibiting a memory phenotype in newborns 21 , perhaps due to antigens encountered in utero (see later). Recent studies in human tissues (described below) have demonstrated that by the end of puberty, lymphoid tissues, mucosal sites and the skin are populated predominantly by memory T cells, which persist through adult life and represent the most abundant lymphocyte population throughout the body 11,23 .…”

Section: Memory T Cell Accumulation Throughout Lifementioning

confidence: 99%

Human memory T cells: generation, compartmentalization and homeostasis

2013

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Memory T cells comprise the most abundant lymphocyte population in the body for the majority of one’s lifetime; however, our understanding of memory T cell generation, function and maintenance mainly derives from mouse studies, which cannot recapitulate the decades-long exposure to multiple pathogens that occurs in humans. Here, we review studies focused on human memory T cells that reveal key properties including subset heterogeneity and diverse tissue residence in multiple mucosal and lymphoid tissue sites. We also discuss how the function and adaptability of human memory T cells depend on spatial and temporal compartmentalization.

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Section: Memory T Cell Accumulation Throughout Lifementioning

confidence: 99%

Human memory T cells: generation, compartmentalization and homeostasis

2013

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“…The maternal influence on immune activation in the child is indicated by the finding that, compared to unexposed uninfected infants, HIV-exposed uninfected neonates show lower CD4+ counts and enhanced levels of immune activation (51). Furthermore the demonstration in the human fetal intestine of large numbers of CD4+CCR5+ T cells, including those with Th17 phenotypes, indicates that infants are indeed susceptible to in utero and/or peri-partum HIV-1 infection (52) and to the vicious cycle of events described above that follow from loss of CD4+ T-cells from the intestinal mucosa. As in adult infection, many studies have shown HIV-infected ART-naïve children show increased levels of plasma markers of microbial translocation (sCD14, LPS, 16srDNA) when compared to healthy controls, the highest levels being observed in the most severely immune-compromised children (46, 47, 53-55).…”

Section: Introductionmentioning

confidence: 97%

“…More recently the anecdotal case of a ‘Visconti’ child was reported, who had maintained aviremia for 12 years having discontinued ART at 6 years of age (98). The tolerogenic immune environment that exists in newborns and through early life, together with the relative paucity of activated memory CD4+ T-cells in the blood that are the targets of HIV infection (52), may tend to prevent the vicious cycle of immune activation that is observed in adult infection, and thereby limit the ability of the virus to establish an extensive viral reservoir of infection. Having said this, as described above, an abundance of activated CCR5+ CD4+ T-cells are present in the fetal gut, and so any limitations the in utero environment impose on the ability of HIV to establish reservoirs of infection in long-lived, latently infected CD4+ T-cells, are only relative.…”

Section: Introductionmentioning

confidence: 99%

Immune activation and paediatric HIV-1 disease outcome

Roider

Muenchhoff

Goulder

2016

Current Opinion in HIV and AIDS

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Purpose of review The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced whilst access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems in adults of chronic inflammation resulting from persistent immune activation even following ART-mediated suppression of viral replication are magnified in children infected from birth. Recent findings Features of immune ontogeny favor low immune activation in early life, whilst specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve non-progressing children exists in whom normal CD4 counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with non-progressing adult infection characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, and that ultimately influence disease outcome, are discussed. Summary Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV.

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“…ϩ T cells was recently reported in the infant gut (14). Infants also exhibit a bias toward Th2 responses (15).…”

Section: Ccr5mentioning

confidence: 99%

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

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Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1

Cited by 77 publications

References 38 publications

Human memory T cells: generation, compartmentalization and homeostasis

Human memory T cells: generation, compartmentalization and homeostasis

Immune activation and paediatric HIV-1 disease outcome

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

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