CD4 help regulates expression of crucial genes involved in CD8 T cell memory and sensitivity to regulatory elements.
J Immunol. 2008 Jul 1;181(1):299-308
Rapetti L, Meunier S, Pontoux C, Tanchot C.
Although the role of CD4 help during memory differentiation has been clearly demonstrated, the mechanisms involved to mediate CD4 help is unknown. In this study, gene analysis shows that unhelped CD8 cells have defects in their three main characteristics of expression; proliferation, survival and cytotoxic functions. This shows that CD4 cells have multiple effects on CD8 memory differentiation.
Link to PubMed abstract
CD4 Percentages and Total Lymphocyte Counts as Early Surrogate Markers for Pediatric HIV-1 Infection in Resource-Limited Settings
Journal of Tropical Pediatrics, 2006 Oct; 52: 346-354.
F Rouet,, A Inwoley, D Ekouevi, I Viho, R Becquet, C Sakarovitch, L Bequet, B Tonwe-Gold, ML Chaix, V Leroy, C Rouzioux, F Dabis and the ANRS 1201/1202 Ditrame Plus Study Group.
This paper looks at %CD4 and total lymphocyte count (TLC) in African children born to HIV-1-infected mothers as useful markers of HIV infection. The authors show data where at 3 months after birth, a threshold of 25% CD4 cells could be used to distinguish HIV infection from those children who were not HIV infected. TLC was of no value. Interesting paper, showing that %CD4 maybe a sensitive cost-effective alternative to plasma RNA copies.
Evidence for extrathymic T cell maturation after thymectomy in infancy.
Clinical and Experimental Immunology, 2006 Sep;145(3):407-12.
Torfadottir H, Freysdottir J, Skaftadottir I, Haraldsson A, Sigfusson G, Ogmundsdottir HM.
This is an interesting paper that looks at extrathymic T cell maturation. Although limited in numbers, this study was able to investigate 8 infants who were thymectomized during heart surgery and compare T cell subsets with control children who were sex and age-matched. Cell subsets were looked at using flow cytometry using panels of antibodies measuring naïve, memory, activated and regulatory T cell markers. Authors conclude that some T cell phenotypes, notably T regulatory subsets, can mature without a thymus.
Increased CD154 Expression in Uninfected Infants Born to HIV-Positive Mothers Exposed to Antiretroviral Prophylaxis.
Viral Immunology, 2006 Sep;19(3):363-72.
Romano MF, Buffolano W, Bisogni R, Russo R, Liuzzi R, Bunders M, Newell ML, Giarrusso PC.
This paper studies the immunostimulatory effects of ART in uninfected HIV-exposed infants receiving either ante- or postnatal therapy. They found that CD4(+) and CD8(+) lymphocytes of HIV-exposed noninfected infants who have been exposed to antiretroviral drugs in foetal life and early life display enhanced CD154 expression on both subsets. Although there was no T cell functional tests performed, it is possible this may mean increased T helper function in response to ART in uninfected infants?
Within and between race differences in lymphocyte, CD4+, CD8+ and neutrophil levels in HIV-uninfected children with or without HIV exposure in Europe and Uganda.
Annals of Tropical Paediatrics, 2006 Sep;26(3):169-79
Bunders M, Lugada E, Mermin J, Downing R, Were W, Thorne C, Newell ML; European Collaborative Study.
This paper looks at large numbers of children born and living in Europe and those children born and living in Uganda, age, gender and genetically matched (children born to Ugandan mothers). Differential counts, total lymphocyte counts and %CD4 and %CD8 T cells were compared. They found differences in neutrophils and %CD4 cells, being lower in children living in Uganda. The authors conclude that nutrition and exposure to micro-organisms affect the developing immune system and account for these differences.
Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy.
Archives of Pediatric Adolescent Medicine, 2006 Aug;160(8):778-87.
Ylitalo N, Brogly S, Hughes MD, Nachman S, Dankner W, Van Dyke R, Seage GR 3rd; Pediatric AIDS Clincial Trials Group Protocol 219C Team.
This paper studies the relationship of HAART and opportunistic infections among 1927 children who were perinataly infected with HIV. They found that a low % CD4 T lymphocytes and a lack of sustained response to HAART, rather than the age or duration of drug treatment, was significantly predictive of opportunistic infection risks.
Administration of Live Varicella Vaccine to HIV-Infected Children with Current or Past Significant Depression of CD4+ T Cells
Journal of Infect Diseases, 2006 Jul 15;194(2):247-55.
Levin MJ, Gershon AA, Weinberg A, Song LY, Fentin T, Nowak B. Pediatric AIDS Clinical Trials Group 265 Team.
This paper explores the vexing issue of immunizing HIV positive children against chicken pox and at what level of CD4 counts would be safe. Children ranging from 1-8 years of age and who had never had chicken pox before (naïve for Varicella Zoster virus, VSV) were given varicella vaccine. The authors show that regardless of CD4 counts in the children, the vaccine was well tolerated and 80% of HIV positive children made antibodies. Thus, children infected with HIV would probably be protected (by the production of antibodies), with a CD4 percent of greater than or equal to 15% and a CD4 count of equal to or greater than 200 cells.
Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children. HIV Paediatric Prognostic Markers Collaborative Study.
AIDS 2006 Jun;20(9):1289-94
This study looks at the risk to progression to AIDS and death within 12 months by investigating absolute CD4 counts. In children older than 4-5 years of age the risk of disease progression increased when the CD4 count fell below 200-330 cells/microl, although the CD4 cell count was less prognostic in younger children. The authors conclude that CD4 criteria used in adults can be extended to children from 4-5 years of age, but not younger.
Outcomes for human immunodeficiency virus-1-infected infants in the United kingdom and Republic of Ireland in the era of effective antiretroviral therapy.
Pediatric Infectious Disease Journal, 2006 May;25(5):420-6.
Doerholt K, Duong T, Tookey P, Butler K, Lyall H, Sharland M, Novelli V, Riordan A, Dunn D, Walker AS, Gibb DM. Collaborative HIV Paediatric Study.
This paper looks at the progression of AIDS and the subsequent death of infected infants in the era of ARV since 1997. CD4 and HIV-1 RNA responses were assessed in 481 infants and the paper shows data where mortality was lowered by giving HAART, but symptomatic disease rates remain high.
European Collaborative Study. CD4 cell response to antiretroviral therapy in children with vertically acquired HIV infection: is it associated with age at initiation?
Journal of Infectious Diseases, 2006 Apr 1;193(7):954-62
Newell ML, Patel D, Goetghebuer T, Thorne C.
This paper explores the early initiation of ART in children and comes from the European Collaborative Study. The study took 131 children ranging from 0.1 to 15 years and showed that there was a benefit of initiating ART before 5 months of age. This appeared to result in a sustained recovery of the CD4 count. Lots of statistics.
Evaluation of p24-based antiretroviral treatment monitoring in pediatric HIV-1 infection: prediction of the CD4+ T-cell changes between consecutive visits.
Journal of Acquired Immune Deficiency Syndrome, 2006 Apr 15;41(5):557-62.
Brinkhof MW, Boni J, Steiner F, Tomasik Z, Nadal D, Schupbach J.
This paper looks at cheaper and affordable methods of evaluating the effectiveness of ART, rather than measuring viral load. This was a small study of 24 children followed over 5 years of ART. Viral loads were measured in parallel with an ultra sensitive p24 assay in heated plasma. The findings appear a bit ambiguous, but the authors conclude that p24 may be more accurate than measuring viral load and certainly cheaper.
Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy
Journal of Allergy Clinical Immunology, 2006 Apr;117(4):748-52.
Saitoh A, Singh KK, Sandall S, Powell CA, Fenton T, Fletcher CV, Hsia K, Spector SA.
This paper provides evidence that new T cells arrive in the blood circulation when children are treated with ART. This was measured by looking at T cell receptor excision circles (TRECs), which indicate recently recruited T cells from the thymus gland. The authors made associations with levels of HIV DNA and the levels of TREC and conclude that the thymus gland is active in producing new CD4 cells when HIV DNA levels are high during ART. The conclusion is that TREC levels are a useful marker of thymus gland function in HIV infected children.
The First 5 Years of the Family Clinic for HIV at Tygerberg Hospital: Family Demographics, Survival of Children and Early Impact of Antiretroviral Therapy
Journal of Tropical Pediatrics, 2006 Feb; 52(1):3-11
N van Kooten Niekerk, M. Knies, J. Howard, H. Rabie, M. Zeier, A. van Rensburg, N. Frans, HS Schaaf, G. Fatti, F. Little and MF Cotton.
This study was aimed at children attending the Family Clinic at Tygerberg Academic Hospital. They study the factors that affect disease progression in children. 432 children were tested and the majority of these children were malnourished. 47 percent of these children were in clinical stage B and two-thirds had moderate or severe CD4 (+) T cell depletion.
