T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.
HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.
Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.|Department of Immunology, University of Washington, Seattle, WA, USA.
M B
MB
Buechler
Department of Epidemiology.
L P
LP
Newman
Department of Global Health, University of Washington, Seattle, WA, USA.|Kenya Medical Research Institute.
B H
BH
Chohan
Research and Programs Department, Kenyatta National Hospital.
A
A
Njoroge
Department of Pediatrics, University of Nairobi, Nairobi, Kenya.
D
D
Wamalwa
Department of Epidemiology.|Department of Global Health, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
C
C
Farquhar
D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002648:Child; D002675:Child, Preschool; D017635:Clonal Anergy / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D007630:Kenya; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008457:Measles / Q000276:immunology* / Q000517:prevention & control; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D061026:Programmed Cell Death 1 Receptor
ART; HIV; T cells; measles; revaccination