Phenotypical and functional characteristics of peripheral lymphocytes in children with common variable immunodeficiency (CVID) and X-linked hypogammaglobulinemia (XLA).

Results

IV. Results

              The total percentage of lymphocytes and CD4/CD8 T cell ratio were slightly but significantly declined both in the CVID and XLA, with lower total abs. lymphocyte count in the CVID but elevated in XLA patients as compared with control, p<0.05. The characteristics of basic lymphocyte subsets were as follow: 1) higher CD3 and CD4+ T cell numbers in the XLA than in the controls and CVID, p<0.05, 2) decreased fluorescence intensity (FI) of CD3 receptor (CD3low) in the CVID (p<0.05) but normal in XLA, 3) CD4low in the XLA with similar tendency in the CVID; decreased abs. number of CD4+ T cells in the CVID as compared with the control and XLA, 4) elevated proportions of CD8 T cells in the XLA (p<0.05) but unchanged in the CVID; CD8high in CVID and XLA with low CD8+ abs. count in the CVID as compared with controls (p<0.05), 5) normal proportions but CD56low and a decrease in abs. count of the NK cells in both groups as compared with the controls, more pronounced in the CVID than in the XLA (p<0.05). (table1). th children groups; also the CD4v/m low boithraompared to the control and group B,  P<0.001. Both in the  group A and B the amount of  CD3+ and CD4+ cells was  significantly reduced (percentage, absolute cell number, p< 0.001). Conversely, the proportion of CD8+ cell subset  was not changed but its absolute number was low in a  group  A (p<0.05) and  normal in a group B. The density of  CD8 receptor in the CD8+ cell subset  was reduced  (group A and B)  as compared to the control (p<0,001). The mean  CD4/CD8 ratio was below 1 (group A),  and slightly above 1 (group B), p < 0,01). The mean number of CD19+ cells   (percentage, absolute number) was low in a group A (p<0,01) but not changed in a group B. Almost  threefold  increase in the  NK cell amount  (percentage, absolute number) was observed both in the group A and B of NBS patients.

The expression of CD45RA and CD45RO isoforms of CD45Ag in the CD4+, CD8+  and CD56+ lymphocyte subsets is presented in the table 2.

The  proportion and absolute number of the "naive" CD4/CD45RA+ lymphocyte subset  was greatly declined (group A, B) as did the density of its CD4 receptor (p< 0.0001). In contrast, the proportion of the "naive" CD8/CD45RA+ cells was not affected but their  absolute number was significantly decreased in a group A p<0,001,  or normal (group B). The mean density of CD8 receptor in the „naive” CD8+ cell subset (group A and B) was  twofold  lower than in the control (P< 0.001), but the mean density of its  RA isoform remained unchanged.   

              Conversely, the mean percentage of "memory" CD4 and CD8+ cell subsets was elevated more than threefold (group A and B, p< 0,01). Furthermore, the absolute number of „memory” CD4+ and CD8+ cell subsets was  increased over twofold in a group A, or even threefold and  fourfold respectively, in a group B. The mean ratio of CD45RA to CD45RO  CD4+ or CD8+ cell subsets was about 15 and 4 times  lower respectively, in both groups of NBS patients, as compared to the control (p <0,001). However, the mean density of  CD4 and CD8 receptors in the CD4+ and CD8+  „memory” cell subsets was unaffected. In contrast,  the mean  density of RO isoform  in the  „memory” CD4+ and CD8+ cell subsets was about twofold higher (group A and B ) than in the control, p< 0,001.       

              In addition to the deficiency of the  "naive" helper T cell subset , and shift from „naive” to „memory” phenotype in the  CD4+ and CD8+ lymphocyte subsets,  the most characteristic phenotypical feature of lymphocytes of NBS patients (group A and B)  was an increase in the  percentage and absolute number of NK  cell subset with unaffected expression (density, percentage) of  both CD45RA isoform and  CD56 receptor. In contrast, the expression of CD45RO isoform in CD56 positive cell subset was increased in NBS (p< 0,05) in terms of the proportion,  the absolute  cell number and declined ratio of  RA+/RO+  CD56+ cells  (table 2).

The whole  CD8+ cell population  consists of at least two subsets, namely: a)  CD3/CD8high T cell with CD8 receptor of high density, and b)  CD3-/CD8low with CD8 receptor of low density, which corresponds to the CD8/CD56+ NK lymphocyte subset (10). Therefore we evaluated  the distribution of CD8 receptors in the CD3/CD8high, CD3-/CD8low and CD8low/CD56+ lymphocyte subpopulations in terms of the percentage of positive  cells and receptors density (table 3).

The mean proportion and absolute number of CD8+ T cell subset  (CD3+/CD8high) was significantly declined in the most of NBS patients  (group A), or only slightly reduced but without statistical significance (group B).  Also the density of CD3 receptors in this T cell subset was not  affected (P>0.05) as did the density of CD8 receptors (p< 0.05).     

              The mean number of CD3-/CD8low lymphocyte subset and the density of its CD8 receptors were significantly higher in the NBS patients (group A and B)  as compared to the control group (p <0,01).

As mentioned above, the CD3-/CD8+ cell subset  corresponds to the subpopulation of CD8+/CD56+ bearing cells.  In the NBS patients this cell subset was significantly elevated both in terms of proportion (group A, B) and absolute cell  number (group B). The mean  density of CD8 and CD56 receptors in the population of CD8+/CD56+ cells was  unchanged. Despite an increase in the proportion  of CD8/CD56+ cell subset (group A,B) and its absolute number (group B) of NBS patients, the mean  ratio of  the percentage of  CD56+ cell subset  to the  CD56/CD8+ cell subset was equal to the control value.