Table 1.
The Role of T cells in SLE and Atherosclerosis
| Statement | Experimental evidence | Clinical evidence |
|---|---|---|
|
| ||
| T cells contribute to atherosclerosis |
EVIDENCE SUPPORTING:
|
|
| T cells are present in atherosclerotic plaques of LDLr−/− and ApoE−/− mice (22) | T cells are present in human atherosclerotic plaques (21,23) | |
| CD4+ T cells transferred into scid/scid, ApoE−/− mice increased atherosclerosis (25) | Th17 cells are present in human atherosclerotic plaques (49) | |
| Atherosclerosis is reduced in CD4−/−, ApoE−/− mice (27) | ||
| Th1 bias results in increased atherosclerosis (28) | ||
| Th17 cells are present in atherosclerotic plaques (48) | ||
| Deficiency or neutralization of IL-17 results in up to 50% reduction in atherosclerosis (50,51) | ||
|
| ||
|
EVIDENCE OPPOSING:
| ||
| Bias towards Th2 reduces atherosclerosis (28) | ||
| Anti-IL17A treatment increased atherosclerosis, rIL-17A treatment decreased atherosclerosis (48) | ||
| Reduced Treg or neutralization of TGFβ increased atherosclerosis (38, 39) | ||
|
| ||
| T cells play a role in SLE pathogenesis |
EVIDENCE SUPPORTING:
|
|
| Depletion of CD4+ T cells beneficial to SLE (29) | SLE T cells are hyperactive and have reduced threshold of activation (31) | |
| Thymectomized NZB/W mice did not develop SLE (30) | Increased survival, resistance to apoptosis by SLE T cells (33) | |
| Activated SLE T cells secrete inflammatory cytokines (32) | Th17 cells and IL-17 are increased in SLE (52) | |
| Th17 cells and IL-17 are increased in SLE (53) | Levels of circulating IL-17 correlate with disease activity (54) | |
| Teff in SLE may become resistant to Treg suppression (46) | IL-17 is increased during active nephritis (52) | |
| Th17/Th1 ratio is dysregulated, with increased Th17 (55) | ||
| Teff in SLE may become resistant to Treg suppression (44,47) | ||
|
| ||
|
EVIDENCE OPPOSING:
| ||
| Treg deficiency results in severe autoimmune disease (40,41) | Treg deficiency results in severe autoimmune disease (40,41) | |
| Treg are reduced in SLE (42) | Treg are reduced in SLE (43) | |
|
| ||
| T cells contribute to increased CVD risk in SLE | In LDLr.S/e mice, atherosclerosis was increased, accompanied by infiltration of CD4+ T cells into atherosclerotic lesions (12,35) | |
T cell subsets can have divergent effects on both atherosclerosis and SLE, with Th1 and Th17 contributing to disease pathogenesis and Treg protecting against disease.