Introduction: Humoral responses to influenza vaccination in transplant recipients are variable. However, little is known about the generation of cell-mediated immunity after vaccination. We conducted a detailed analysis of T cell subsets, monocytes, and B cells in a cohort of organ transplant patients who received influenza vaccine.

Methods: Adult transplant patients were recruited as part of a large influenza vaccine trial. In a subset of patients, peripheral blood mononuclear cells were collected pre- and 1 month post-vaccination. We characterized Influenza H1N1-, H3N2-, B-specific T-cell responses (IFNΓ+/IL4+/CD69+), T-follicular helper cell frequencies (TFH, CXCR5+CD4+), B-cell activation (CD69/HLA-DR/CD86) and monocyte-activation (HLA-DR/CD86) using flow-cytometry. Results were correlated with clinical data and humoral vaccine response.

Results: We analyzed 39 patients including kidney (17), liver (4), lung (15), and heart (3). Median time from transplant to vaccination was 3.5 years (range 0.26-22.3). Overall, after vaccination, CD4+T-cell frequencies of CD69+IFNΓ+ cells stimulated with H1N1 ranged 0.05-2.92% and CD69+IL4+ cells ranged 0.05-2.42%. In patients who seroconverted to H1N1, the pre to post-vaccination increase in CD69+IFNΓ+ T cells was 2.5-fold vs. 1.0-fold in serologic nonresponders to vaccine (p=0.002). Similarly, for CD69+IL4+ cells, patients who seroconverted had a median increase of 4.0-fold vs. 1.0-fold in nonresponders (p<0.001). Similar trends were seen for the B-strain. In patients receiving high dose MMF (>2g/day), trends towards lower cellular responses to H1N1 were noted. For example, IFNΓ+ T-cell frequencies for H1N1 were a median of 0.5% vs. 0.23% (p=0.07) in patients on <2g/d vs. >2g/d MMF. Similarly, IL4+ T-cell frequencies were 0.66% vs. 0.13% (p=0.001) respectively. Compared to thoracic transplant recipients, kidney transplants had better IFNΓ+ and IL4+ T-cell responses to vaccine (3.2 fold increase IFNΓ+ CD4 cells in kidney vs. 1.0-fold in thoracic transplant). Also, the frequency of T-follicular helper cells correlated with seroprotection to H1N1 (12.8% vs. 8.4%; p=0.064).

Conclusions: Overall, transplant recipients have a poor cellular immune response to influenza vaccine that generally correlates with seroconversion. High doses of MMF reduced cellular responses. Detailed cellular immunity analysis identifies potenail novel biomarkers to predict vaccine response.

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