Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine.
The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection, in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n = 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonresponders (n = 8). In coculture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Suresh
S
Pallikkuth
Anita
A
Parmigiani
Sandra Y
SY
Silva
Varghese K
VK
George
Margaret
M
Fischl
Rajendra
R
Pahwa
Savita
S
Pahwa
D000328:Adult; D000917:Antibody Formation / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000097:blood / Q000150:complications / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D017211:Treatment Failure; D055815:Young Adult
D007252:Influenza Vaccines