Subsets of memory CD4+ T cell and bactericidal antibody response to Neisseria meningitidis serogroup C after immunization of HIV-infected children and adolescents.

Meningococcal disease is endemic in Brazil, with periodic outbreaks and case fatality rates reach as high as 18 to 20% of cases. Conjugate vaccines against meningococci are immunogenic in healthy children. However, we have previously shown a poor bactericidal antibody response to a Men C conjugate vaccine in Brazilian HIV-infected children and adolescents after a single vaccine administration. The goal of the present work was to investigate associations between bactericidal antibody response induced by MenC vaccine and the frequency and activation profile (expression of CD38, HLA-DR and CCR5 molecules) of total CD4+ memory T cell sub-populations in HIV-1-infected children and adolescents. Responders to vaccination against MenC had a predominance (about 44%) of CD4+ TINTERMEDIATE subset followed by TTRANSITIONAL memory subset (23 to 26%). Importantly, CD4+ TINT frequency was positively associated with bactericidal antibody response induced by vaccination. The positive correlation persisted despite the observation that the frequency TINT CD38+HLA-DR+ was higher in responders. In contrast, CD4+ TCENTRAL MEMORY (TCM) subset negatively correlated with bactericidal antibodies. In conclusion, these data indicate that less differentiated CD+ T cells, like TCM may be constantly differentiating into intermediate and later differentiated CD4+ T cell subsets. These include CD4 TINT subset which showed a positive association with bactericidal antibodies

Strategy of analysis of Flow Cytometer data from one representative experiment with PBMC samples of HIV infected children.

<p>(A) Were used high Quality Parameters: (Time x PE-to check laser status; Singlets-to exclude the doublets cells; SSC x FSC- to choose lymphocytes subset; Live/Dead-to exclude the dead cells; gate SSC x CD3- to chose T lymphocytes and gate CD4 x CD8- to separate in CD4 and CD8 T subsets, then b Naïve/Memory subsets and cellular activation were evaluated in CD4 T Cells and CD8 T Cells, (B) Naïve/Memory CD4⁺ Subsets were classified through differentiated expression of three markers (CD45RA, CD27 and CCR7): 1- Naïve (CD45RA⁺CD27⁺CCR7⁺); 2- Central Memory (CD45RA⁻CD27⁺CCR7⁺); 3- Transitory Memory (CD45RA⁻CD27⁺CCR7⁻); 4- Intermediary Memory (CD45RA⁺CD27⁺CCR7⁻); 5- Effector Memory (CD45RA⁻CD27⁻CCR7⁻); 6- Effector (CD45RA⁺CD27⁻CCR7⁻); Cellular Activation were characterized through expression of CD38, HLA-DR and CCR5.</p

Triple positive CD4⁺ T cells negatively correlates with bactericidal antibody titers.

<p>CD4⁺ T_NAIVE (A) and T_EM (B) T cells with CD38⁺DR⁺CCR5⁺ phenotype correlates negatively with post-vacciantion bactericidal titers (V2). Correlations were analyzed using Sperman rank test.</p

Frequency (median) of CD4⁺ T cell subsets expressing different combinations of CD38, HLA-DR and CCR5 molecules in PBMC collected before vaccination (V1).

<p>Seroconversors (Sc+), Non-seroconversors (Sc−).</p><p>*p-value <0.05 comparing Sc- versus Sc+</p><p>Frequency (median) of CD4⁺ T cell subsets expressing different combinations of CD38, HLA-DR and CCR5 molecules in PBMC collected before vaccination (V1).</p

Predominance of CD4⁺ T_INT memory subset among HIV⁺ seroconverters.

<p>Frequency and median (lines) of CD4⁺ T_Naive (A), T_CM (B), T_TM (C), T_INT (D), T_EM(E) and T_Eff (F) subpopulations in seroconverters (Sc+, closed symbols) and non-seroconverters (Sc-, open symbols) before (V1) and after (V2) vaccination.</p