Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

Ben-Smith, Anne; Gorak‐Stolinska, Patricia; Floyd, Sian; Weir, Rosemary E.; Lalor, Maeve K.; Mvula, Hazzie; Crampin, Amelia C.; Wallace, Diana L.; Beverley, Peter C. L.; Fine, Paul E. M.; Dockrell, Hazel M.

doi:10.1186/1471-2334-8-139

Cited by 43 publications

(40 citation statements)

References 42 publications

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“…Finally, it might reflect early life environmental exposure to pathogens. This is in keeping with the differences in T cell memory subsets, especially higher numbers of T cells with an effector memory immunophenotype and lower numbers of T cells with a central memory immunophenotype, as described in Malawian as compared with UK adolescents, despite no differences in lymphocyte populations in cord blood from these populations 19. It has been suggested that these differences result from greater exposure to early-life infections in the African environment 20.…”

Section: Discussionsupporting

confidence: 82%

A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children

Lucas

Nicol²,

McKinnon

et al. 2010

Thorax

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Background Diagnosis of latent tuberculosis infection (LTBI) is a cornerstone of the health assessment of resettled high incidence populations, particularly in children. Two blood-based interferon g release assays (IGRAs), T-SPOT.TB and QFT-Gold in-tube (QFT-GIT), have greater sensitivity and specificity than the tuberculin skin test (TST), but their performance as screening tools for LTBI in children, especially refugee children, remains unclear. Methods 524 African and ethnic Burmese children, including 107 under 3 years of age, were prospectively enrolled in a comparison of the T-SPOT.TB and QFT-GIT. The TST was also performed in 342 of the children. Results The T-SPOT.TB and QFT-GIT had similar rates of positivity (8% and 10%, respectively) and showed good concordance when both tests gave definitive results (k¼0.78; p<0.0001). However, the IGRAs had significant failure rates: 15% of QFT-GIT gave indeterminate results due to failed mitogen response and 14% of T-SPOT.TB results were inconclusive, largely because of insufficient mononuclear leucocyte yields. Failure of the QFT-GIT mitogen response was associated with African ethnicity and co-morbid infections, particularly with helminths. The TST results showed poor concordance (w50%) with both IGRAs. Conclusions It is reasonable to screen using either IGRA with follow-up by the alternative if the test fails. In general, the QFT-GIT is the preferred option for nonAfrican populations but the T-SPOT.TB is recommended when there are epidemiological and/or clinical high risk factors for TB infection. However, both IGRAs have methodological and performance characteristics that limit their usefulness in refugee children, highlighting the need for continued development of screening strategies.

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Section: Discussionsupporting

confidence: 82%

A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children

Lucas

Nicol²,

McKinnon

et al. 2010

Thorax

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“…One main inducer of constant immune activation is the more frequent exposure to infectious diseases in Entebbe, which lies on the shore of Lake Victoria, when compared with the Lausanne population. Chronic or acute inflammatory conditions, including pathogenic viral, bacterial, fungal, or parasitic infections, might play a role in this immune activation (49,50). Of note, we did not observe significant differences in YF-17D NAb titers between individuals who reported a coinfection as an adverse event after vaccination and those that did not.…”

Section: Discussionmentioning

confidence: 45%

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Muyanja¹,

Ssemaganda²,

Ngauv³

et al. 2014

J. Clin. Invest.

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Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Conclusion.Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.Trial registration. Registration is not required for observational studies.

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“…It has been suggested that, at least among non-HIV-infected individuals, immune responses are induced and maintained very differently in young Africans than in age-matched European controls, due to the earlier and greater exposure to antigenic challenges 18. This was true for exposure to CMV in particular and although it is not clear how this might be responsible for more resistance to the virus in the immunocompromised state, this difference in environmental exposure in early life may play a role in the putative protection against CMV retinitis among Africans.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of cytomegalovirus retinitis in Tanzanians with low CD4 levels

Nirwoth

Hall

Lewallen³

2010

British Journal of Ophthalmology

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This study demonstrates that AIDS patients in Tanzania do survive into the stage of severe immunosuppression, and that even among this group CMV retinitis is very uncommon. This supports previous studies reporting low prevalence of CMV where CD4 counts were not available. Differences in immune response in AIDS patients in different settings may depend on environmental exposure to specific viruses early in life.

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Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

Abstract: Background: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years.

Cited by 43 publications

References 42 publications

A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children

A prospective large-scale study of methods for the detection of latent Mycobacterium tuberculosis infection in refugee children

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Prevalence of cytomegalovirus retinitis in Tanzanians with low CD4 levels

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