AUTHOR=Leibinger Evelin A. , Pauler Gábor , Benedek Noémi , Berki Tímea , Jankovics István , McNally Richard , Ottóffy Gábor 

TITLE=Baseline CD3+CD56+ (NKT-like) Cells and the Outcome of Influenza Vaccination in Children Undergoing Chemotherapy

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.690940

DOI=10.3389/fimmu.2021.690940

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>In children undergoing chemotherapy yearly influenza vaccination is recommended by treatment protocols. We investigated the relationship between cellular immunity and the antibody response to inactivated influenza vaccines.</p></sec><sec><title>Methods</title><p>25 patients (age: 2-18 years) undergoing chemotherapy for different malignancies participated in our study. Flow cytometric detection of peripheral blood lymphocyte subpopulations together with hemagglutination inhibition antibody titers were measured before and 21-28 days after vaccination. We examined the ratio and total numbers of CD3+, CD4+, CD8+ T cells, activated helper (CD3+CD4+CD25<sup>low</sup>), regulatory (CD3+CD4+CD25<sup>high</sup>), naive (CD3+CD45RA+) and memory (CD3+CD45RO+) T cells, CD56+NK, and CD3+CD56+ (NKT-like) cells. Relationships between specific antibody responses (seroprotection, seroconversion, geometric mean titer (GMT), geometric mean fold increase (GMFI)) and the ratios and counts of lymphocyte subpopulations were evaluated using one-way ANOVA and the paired sample t test after dichotomization according to age-related reference values.</p></sec><sec><title>Results</title><p>Patients with CD4+ lymphocyte levels in the normal age-specific range showed significantly better response regarding postvaccination GMT elevation for H1N1 and H3N2 strains (97.52 <italic>vs</italic>. 19.2, p=0.019, 80 <italic>vs</italic>. 14.43, p=0.021, respectively). GMFI results were significant only against B strain (2.69-fold <italic>vs</italic>. 1.23-fold, p=0.046). Prevaccination CD3+CD56+ (NKT-like) cells above predicted values according to age showed significant associations both in postvaccination GMT elevation (H1N1: 75.11 <italic>vs</italic>. 14.14, p=0.010; H3N2: 62.18 <italic>vs</italic>. 11.22, p=0.012; B: 22.69 <italic>vs</italic>. 6.67, p=0.043) and GMFI against all three strains (H1N1: 3.76-fold <italic>vs</italic>. 1.06-fold, p=0.015; H3N2: 2.74-fold <italic>vs</italic>. 1, p=0.013; B: 2.57-fold <italic>vs</italic>. 1, p=0.008). By one-way ANOVA, we found a positive relation between absolute lymphocyte cell count above 1000/µl and the postvaccination GMT elevation against H3N2 (12.81 vs. 56.56, p=0.032), and GMFI regarding H1N1 (1.22-fold <italic>vs</italic>. 3.48-fold, p=0.044).</p></sec><sec><title>Conclusions</title><p>In addition to verifying the predictive value of absolute lymphocyte count above 1000/µl, our results suggest an association between NKT-like cell counts and the specific antibody response against all three investigated influenza strains in highly immunosuppressed patients. Furthermore, prevaccination CD4+ lymphocyte levels in the normal age-specific range may influence seroresponse.</p></sec>