The Distribution and Immune Profile of T Cell Subsets in HIV-Infected Children from Uganda.
Abstract T cell activation is an important mechanism in HIV-associated immune depletion. We have previously demonstrated an association between the hyperactivation of CD4(+) and CD8(+) T cells and low CD4 status in HIV-infected Ugandan children. In this study, we explore differences in activation between naive and memory T cells in HIV-infected Ugandan children. A significant correlation between CD4- and CD8-mediated immune activation and CD4 status was observed only in the memory T cells. Antiretroviral (ART) untreated and treated HIV-positive and HIV-negative children displayed similar profiles of activation and distribution within the CD4(+) naive T cells. In contrast, significantly higher immune activation of the memory CD4(+) T cell subset was seen in ART-untreated children when compared to ART-treated or HIV-negative children. ART-mediated viral suppression led to the correction of CD4(+) immune activation to levels seen in uninfected children but did not increase the size of the memory CD4(+) T cell population. High levels of CD8(+) immune activation were also found in both naive and memory cell subsets. Antiretroviral treatment led to the normalization of CD8(+) T cell activation but did not correct the distribution of naive CD8(+) T cells. We also assessed PD-1 expression on CD8(+) T cells as a measure of immune dysfunction. Upregulation of PD-1 was highest in untreated children but persisted in ART-treated children compared to uninfected children. The mechanisms of immunopathogenesis in pediatric HIV infection likely involve distinct contributions from individual naive and memory T cells subsets.
Ssewanyana
Isaac
I
Joint Clinical Research Centre , Kampala, Uganda.
Baker
Chris A R
CA
Ruel
Theodore
T
Bousheri
Stephanie
S
Kamya
Moses
M
Dorsey
Grant
G
Rosenthal
Philip J
PJ
Charlebois
Edwin
E
Havlir
Diane
D
Cao
Huyen
H
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007223:Infant; D061026:Programmed Cell Death 1 Receptor; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D014454:Uganda
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor