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17-03-2013 | Immunology | Article

T cell receptor profile in immune response to flu vaccine identified


Free abstract

medwireNews: Researchers have identified a profile of receptors present on T cells that induces the protective antibody response to influenza vaccine.

"Our study shows that the induction of ICOS+CXCR3+CXCR5+CD4+ T cells represents one of the key immunological events associated with protective antibody responses after seasonal influenza vaccination," say Hideki Ueno (Baylor Research Institute, Dallas, Texas, USA) and colleagues.

T cells expressing this combination of receptors emerge in the blood 7 days after vaccination and induce memory B cells to produce influenza-specific immunoglobulins (Igs), reports the team.

The findings come from a study of two healthy cohorts, one of which comprised 12 adults, and the other 19 children. After administering a nonadjuvenated trivalent split seasonal influenza vaccine to both cohorts, the researchers found that the frequency of CD4+ T cells expressing ICOS (inducible costimulator) increased and peaked at day 7.

This upregulation of ICOS was largely confined to CXCR5+CD4+ T cells, and within this subgroup, only in cells that coexpressed CXCR3.

As the influenza vaccine provides protection mainly by antibodies binding hemagglutinin, the researchers measured hemagglutinin inhibition and virus neutralization titers in blood samples collected from the participants at baseline and at day 28.

As reported in Science Translational Medicine, the increase of ICOS+CXCR3+CXCR5+CD4+ T cells in the participants' blood positively correlated with increases in global antibody titers among both children and adults.

Furthermore, the increase of blood plasmablasts strongly correlated with the increase in ICOS+CXCR3+CXCR5+CD4+ T cells in the adult cohort. A trend for the increase of these T cells to correlate with the increase in plasmablasts was also observed among the children, although this did not reach significance.

Further analysis showed that the ICOS+CXCR3+CXCR5+CD4+ T cells expressed several cytokines including interferon-gamma in 70% of the T cells, interleukin (IL)-2 in 50%, and IL-21 in 40%, while all three cytokines were expressed in 20%.

On culturing ICOS+CXCR3+CXCR5+CD4+ T cells with B cells and staphylococcal enterotoxin B, naïve B cells did not proliferate or differentiate into antibody-secreting cells. However, memory B cells were induced to differentiate into plasma cells.

Next, the researchers co-cultured the ICOS+CXCR3+CXCR5+CD4+ T cells with memory B cells loaded with influenza virus and found that this induced the differentiation of memory B cells into plasma cells that produced influenza-specific IgG.

"Together these observations show that ICOS+CXCR3+CXCR5+CD4+ T cells induced by influenza vaccination recognize influenza antigens and are capable of inducing memory B cells to produce influenza-specific Igs," writes the team.

By Sally Robertson, medwireNews Reporter

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