CD8 T cell effector maturation in HIV-1-infected children.
HIV-1 infection generates maturational responses in overall CD4 and CD8 T cell populations in adults, with elevated expression of lytic effector molecules perforin and granzyme B, and reduced expression of CCR7 and CD45RA. Here, we have found that these marked effects were significantly less pronounced in children, both in terms of the skewed CCR7/CD45RA expression profile as well as the increased perforin expression. Similar to adults, HIV-specific CD8 cells in children were largely CD27+ CD45RA- and lacked perforin. However, one pediatric subject with late-stage infection displayed robust expansion of Gag 77-85-specific CD8 T cells which were perforin+ and lytic, but lacked expression of CD27 and IFNgamma. Our data indicate that the T cell effector maturation induced by HIV-1 infection is markedly weaker in children as compared to adults. The data also suggest, however, that the perforin-deficient state of HIV-specific CD8 T cells in children may be reversible.
Jordan
Kimberly A
KA
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA.
Furlan
Scott N
SN
Gonzalez
Veronica D
VD
Karlsson
Annika C
AC
Quigley
Máire F
MF
Deeks
Steven G
SG
Rosenberg
Michael G
MG
Nixon
Douglas F
DF
Sandberg
Johan K
JK
D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D015683:Gene Products, gag / Q000276:immunology; D053804:Granzymes; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D054299:env Gene Products, Human Immunodeficiency Virus
C515370:CCR7 protein, human; D015683:Gene Products, gag; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D054299:env Gene Products, Human Immunodeficiency Virus; C473991:p17 gag peptide, human immunodeficiency virus; D054353:Perforin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases