Table I.
Immunologic parameters I: a/Peripheral blood lymphocyte markers and b/Mitogen stimulated T cell proliferation
| Age | 2.8 year | 3 year | (NV) |
|---|---|---|---|
| (Post-rituximab) | |||
| a/Lymphocytes (cells/μl) | 3602 | 909 | (2–8000) |
| CD3+T cells (cells/μl) | 1885 | 721 | (900–4500) |
| CD3+/CD8+T cells (cells/μl) | 714 | 250 | (300–1600) |
| CD3+/CD4-/CD45RA+/CD27+ (% T cells) | 4 % | 6 % | |
| CD3+/CD4-/CD45RA+/CD27+ (cells/μl) | 75 | 43 | |
| CD3+/CD4-/CD45RA+/CD27- (% T cells) | 0 | 0 | |
| CD3+/CD4+T cells (cells/μl) | 459 | 243 | (500-2400) |
| CD3+/CD4+/CD45RA+/CD27+ (% T cells) | <1 % | <1 % | |
| HLA-DR+/CD3+T cells (% T cells) | 50 % | 26 % | |
| T cell receptor alpha/beta (% T cells) | 43 % | n/a | |
| T cell receptor gamma/delta (% T cells) | 57 % | n/a | |
| CD19+B cells (cells/μl) | 1064 | 0 | (200–2100) |
| CD19+CD27-IgD+ (% B cells) | 71 % | n/a | |
| CD19+CD27+IgD+ (% B cells) | 22 % | n/a | |
| CD19+CD27+IgD- (% B cells) | 4 % | n/a | |
| CD3-/CD56+/CD16+ NK cells (cells/μl) | 615 | 172 | (100–1000) |
| MHC class I and II expression | Normal | ||
| CD40 expression on B cells | Normal | ||
| b/Mitogen stimulated T cell proliferation | (Control) | ||
| Background (cpm) | 2695 | (2741) | |
| PHA | 6429 | (165591) | |
| Anti-CD3 | 106910 | (142813) | |
| PMA+Ionophore | 67039 | (154643) | |
(CD3+/CD4+/CD45RA+/CD27+)—markers for ‘naïve’ CD4+T cells; (CD3+/CD4-/CD45RA+/CD27+)—markers for ‘naïve’ CD8+ (CD4-)T cells; (CD3+/CD4-/CD45RA+/CD27-)—markers for “effector” CD8+ T cells
Profound T cell deficiency is demonstrated by complete absence of CD4+ naïve T cells and very low numbers of CD8+ ‘naïve’ T cells, so that most of the present T cells are of the memory population. This is confirmed by the functional in vitro tests of T cell proliferation showing strikingly reduced proliferation to PHA, but preserved capacity to proliferate to anti-CD3 and PMA mitogens. No antigen-specific T cell proliferation assays were performed. Severe T cell dysregulation is demonstrated by inverted CD4+/CD8+ ratio, very high percentage of ‘activated’ (CD3+/HLA-DR+) T cells, moderate oligoclonality of T lymphocytes expressing TCR-alpha/beta (as shown in Fig. 2), with unusually high proportion of T lymphocytes expressing TCR-gamma/delta (usually <10 %) (no clonality studies of this cell population were performed). Some of these features may be due to the chronic viral (EBV) infection, although there is a complete lack of the ‘effector’ CD8+ T cell population (CD45RA+/CD27-) which would otherwise be expected to be expanded
CD cluster of differentiation; NK natural killer; HLA human leukocyte antigen; MHC major histocompatibility complex; PHA phytohaemmaglutinin; PMA pokeweed mitogen; cpm counts per minute; IL interleukin