Table 2.

Effects of RTX in Selected T-Cell–Mediated Diseases.

Disease	Effect of RTX
RA	1. T-cell depletion, mainly of Th CD4+ cells, associated with clinical response.51-53 Another study failed to observe T-cell depletion54 2. Inhibition of CD4+ T-cell activation and inhibition of T cells and Mϕ in synovial tissue55 3. Decreased RANKL expression in synovium and serum56 suggesting inhibition of Th cell activity 4. Decreased Mϕ counts and activity53,55,57,58 5. Decreased cytotoxic lymphocytes and mature NK cells and a simultaneous upregulation of activated NK cells59,60 6. Decreased IL-15 and IL-17. Clinical improvement may be associated with IL-15/memory T-cell–related mechanisms.61 (IL-15 is known to expand and activate NK cells.) 7. Decreased IL-2, IL-6, IL-7, and IL-10 serum levels62 8. Decreased production of IFN-γ and IL-1β by T cells55 9. Downregulation of genes involved in immunoglobulins, chemotaxis, leukocyte activation, and immune responses with upregulation of genes involved in TGF-β pathway in synovial tissue63 10. Decreased MMP-1, MMP-3, MMP-9 in serum64 likely related to decreased Mϕ count/activity
SLE	1. Possible inhibition of T-cell co-stimulation65-69 2. Decreased memory T cells relative to naive T cells69 3. Decreased expression of CD19, CD21, and BR3 (receptor for the B-cell activating cytokine B-cell activating factor, BAFF, BAFF) on the residual B cells and after B-cell recovery65 4. Decreased percentage of CD69+CD4+T cells (activated T cells) and serum TNF-α level65 5. Shift of the Th1/Th2 balance toward Th165 6. Increased Treg cell number and their regulatory function66 7. Increased activated NK and natural killer T cells70 8. Increased activated CD4 and CD8 T cells, in contrast to other studies71
ITP	1. Immediate response to RTX while autoantibodies are still present72 2. Normalized increased Th1/Th2 ratio73 3. Restored number and regulatory function of Treg cells74
MS	1. Therapeutic effects without changes in serum or CSF antibody levels75-79 2. Decreased T-cell number and proinflammatory cytokines in CSF75-82 3. Reduction in Th1 and Th17 cells and diminished proinflammatory responses of both CD4 (Th1 and Th17) and CD8 T cells mediated by B-cell lymphotoxin and TNF-α secretion80 4. Inhibition of B-cell–dependent T-cell proliferation and Th17 differentiation82 5. Transient decrease in CD4+ and CD8+ T cells in blood83 6. Depletion of increased CD20dim T cells (either CD4+ or CD8+)84
DM1	1. Although anti–T-cell therapies (eg, anti-CD3 antibody) are effective in treatment of DM1,85 RTX was also shown to be helpful in new-onset DM186 2. Reduction in autoantibody production or autoreactive B-cell counts87 3. Increased Treg cells in short term86 4. Modification of the B7-2/CD28 co-stimulation pathway that plays a critical role in priming islet-reactive Th cells88

Note. RTX = rituximab; RA = rheumatoid arthritis; CD = Cluster of differentiation; (comment: again, CDs are standard abbreviations and much more known than the cluster of differentiation); RANKL = receptor activator of nuclear factor kappa–B ligand; NK = natural killer; IL = interleukin; IFN = interferon; TGF = transforming growth factor; MMP = matrix metalloproteinase; SLE = systemic lupus erythematosus; BAFF = B-cell activating factor; BR3 = BAFF receptor 3; TNF = tumor necrosis factor; ITP = idiopathic thrombocytopenic purpura; MS = multiple sclerosis; CSF = cerebrospinal fluid; DM1 = type 1 diabetes mellitus.