Functional state of CD4+ and CD8+ T lymphocytes and their role in the slow progression of HIV infection in pediatric patients

Alfonzo, Miguel; Diaz, Alexandra; Siciliano, Luigina; Lopez, M.; Hung, Alida; García, Juan Félix

doi:10.2223/jped.2183

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Children infected with HIV by vertical transmission, according to a recent study, exhibit a bimodal clinical progression. Thus, 10-30% of patients, called rapid progressors, begin to show symptoms of AIDS in their first year of life, and a small group of patients, called slow progressors, remain asymptomatic for many years and can even reach school age unaffected [8]. …”

Section: Discussionmentioning

confidence: 99%

Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória, Brazil

et al. 2013

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BackgroundStudying diseases associated with AIDS is essential for establishing intervention strategies because comorbidities can lead to death. The objectives were to describe the frequency of comorbidities and verify their distribution according to demographic, epidemiological and clinical data as well as to classify diseases in children and adolescents with AIDS in Vitória, Brazil. MethodsA retrospective cohort study was conducted among children with AIDS, as defined according to the criteria established by the Ministry of Health, who acquired HIV via vertical transmission, were aged 0 to 18 years, and were monitored at a referral hospital from January 2001 to December 2011. ResultsA total of 177 patients were included, of whom 97 were female (55%). There were 60 patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50 patients (28%) ≥6 years of age included at the time of admission to the Infectious Diseases Ward. Regarding clinical-immunological classification, 146 patients (82.5%) showed moderate/severe forms of the disease at the time of admission into the Ward, and 26 patients (14.7%) died during the study. The most common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%), lymphadenopathy (68.4%) and persistent fever (32.8%). The most common comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%), recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An association between severe clinical-immunological classification and admission to the Ward for children aged less than one year old was found for several comorbidities (p<0.001). ConclusionDelayed diagnosis was observed because the majority of patients were admitted to the Infectious Diseases Ward at ≥1 year of age and were already presenting with serious diseases. The general paediatrician should be alert to this possibility to make an early diagnosis in children infected with HIV.

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Section: Discussionmentioning

confidence: 99%

Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória, Brazil

et al. 2013

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“…This pleiotropic cytokine is crucial for the development and homeostasis of T-cells, promotes antigen-specific expansion and memory formation (41–44), and can reverse T-cell exhaustion (45). Immune failure in both adult and pediatric HIV infection is associated with perturbations in IL-7 signaling (46, 47) and reduced responsiveness (48, 49). In adult long-term non-progressors, IL-7R (CD127) expression is preserved on central memory and effector memory CD4 T-cell compartments when compared to untreated progressors (50).…”

Section: Introductionmentioning

confidence: 99%

Increased Regulatory T-Cell Activity and Enhanced T-Cell Homeostatic Signaling in Slow Progressing HIV-infected Children

et al. 2019

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Pediatric slow progressors (PSP) are rare ART-naïve, HIV-infected children who maintain high CD4 T-cell counts and low immune activation despite persistently high viral loads. Using a well-defined cohort of PSP, we investigated the role of regulatory T-cells (T REG ) and of IL-7 homeostatic signaling in maintaining normal-for-age CD4 counts in these individuals. Compared to children with progressive disease, PSP had greater absolute numbers of T REG , skewed toward functionally suppressive phenotypes. As with immune activation, overall T-cell proliferation was lower in PSP, but was uniquely higher in central memory T REG (CM T REG ), indicating active engagement of this subset. Furthermore, PSP secreted higher levels of the immunosuppressive cytokine IL-10 than children who progressed. The frequency of suppressive T REG , CM T REG proliferation, and IL-10 production were all lower in PSP who go on to progress at a later time-point, supporting the importance of an active T REG response in preventing disease progression. In addition, we find that IL-7 homeostatic signaling is enhanced in PSP, both through preserved surface IL-7receptor (CD127) expression on central memory T-cells and increased plasma levels of soluble IL-7receptor, which enhances the bioactivity of IL-7. Combined analysis, using a LASSO modeling approach, indicates that both T REG activity and homeostatic T-cell signaling make independent contributions to the preservation of CD4 T-cells in HIV-infected children . Together, these data demonstrate that maintenance of normal-for-age CD4 counts in PSP is an active process, which requires both suppression of immune activation through functional T REG , and enhanced T-cell homeostatic signaling.

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“…In the early stage of HIV infection, the immune system may not be seriously damaged and may be in the condition of stress response state. During such phase, uncontrolled replication of HIV-1 infection leads to activations of the CD8 + T lymphocytes (which can inhibit HIV replication by cytolytic and noncytolytic responses) and increases the concentration of cytokines such as IFN- γ and IL-10 [ 42 , 43 ]. Earlier studies demonstrated a correlation of maintaining the CD8 + T lymphocyte immune profile with a slow progression of HIV-1 infection [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Dysfunction and Coinfection with Human Immunodeficiency Virus andSchistosoma japonicumin Yi People

Xiao

Yang

et al. 2018

Journal of Immunology Research

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Objective To explore the association between infections with HIV and Schistosoma japonicum, and to determine the influences of the HIV-S. japonicum coinfections on the immune system of Yi people. Methods A block design study was conducted in a Yi county in southwestern China, one of the endemic areas of both HIV/AIDS and S. japonicum in China. All participants were screened for HIV antibodies and S. japonicum antibodies (SjAb) and were classified into four groups: HIV(+)/S. japonicum(−), HIV(−)/S. japonicum (+), HIV(+)/S. japonicum(+), and HIV(−)/S. japonicum(−). Results There were significant differences among the four groups in both CD4+ T lymphocytes and CD8+ T lymphocytes, but no significant difference in CD3+ T lymphocytes. Both the CD4+ T lymphocyte counts and the ratio of CD4+/CD8+ were lower in HIV-infected people compared with those uninfected. People infected with S. japonicum had increased CD4+ T lymphocyte counts but reduced CD8+ T lymphocyte counts. Similarly, the ratio of CD4+/CD8+ was higher in S. japonicum-infected people compared with those uninfected. People coinfected with HIV and S. japonicum had lower CD4+ T lymphocyte counts, lower ratio of CD4+/CD8+, and higher CD8+ T lymphocyte counts compared with those infected with HIV only or S. japonicum only. People infected with HIV only and those coinfected with HIV and S. japonicum had a higher level of IFN-γ compared with people with no infection. There were no significant differences between people infected with HIV only and with S. japonicum only in the levels of IFN-γ and IL-10. Conclusions People coinfected with HIV and S. japonicum might have a suppressed immune function because of a decrease in CD4+ T lymphocyte counts, a lowered ratio of CD4+/CD8+, and an increase in CD8+ T lymphocyte counts. Coinfection with HIV and S. japonicum would alter the level of IFN-γ in plasma.

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Functional state of CD4+ and CD8+ T lymphocytes and their role in the slow progression of HIV infection in pediatric patients

Cited by 4 publications

References 27 publications

Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória, Brazil

Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória, Brazil

Increased Regulatory T-Cell Activity and Enhanced T-Cell Homeostatic Signaling in Slow Progressing HIV-infected Children

Immune Dysfunction and Coinfection with Human Immunodeficiency Virus andSchistosoma japonicumin Yi People

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