Background: The role and the origins of T CD28null lymphocytes in arthritis are still somewhat controversial. Objectives: To correlate TCR-zeta chain and ZAP-70 levels to CD28 expression in T lymphocytes of arthritis patients. Methods: We studied by flow cytometry CD28, TCR-zeta and ZAP-70 expression in T lymphocytes from peripheral blood (PB) and synovial fluid (SF) of 25 arthritis patients (16 RA, 5 PsA, 4 microcrystal arthritis; M/F:14/11; mean age 56.0±18.4). Results: PB CD8CD28null lymphocytes were more abundant than in SF (27.6±1 vs 41±23.3%; p 0.009), and higher in females (32.9±21.7 vs 53.5±20.9%; p 0.04). Both PB CD4CD28null and CD8CD28null were more frequent in those with cardiovascular comorbidities (21±15.4 vs 7.0±5.2%, p 0.003, and 60.6±17.5 vs 34±21.3%, p 0.02, respectively). Both PB CD8CD28null and CD4 CD8CD28null directly correlated with ESR (p 0.01, r +0.55, and p 0.002, r +0.66, respectively) and age (p 0.03, r +0.45, and p 0.07, r +0.40, respectively). Although PB total CD28null lymphocytes seemed not to be related to acute joint inflammation, the percentages of cells expressing intermediate TCR-zeta levels among CD4CD28null and CD8CD28null lymphocytes (CD28nullTCR-zetaint), both in PB and SF, directly correlated with arthritis activity (ESR, CRP, SF leukocyte count and neutrophil percentage, swollen joint count, DAS44 in RA patients). Instead, CD28null lymphocytes expressing high TCR-zeta levels (CD28nullTCR-zetabright) inversely correlated with activity indices. Finally, we observed that CD28 down-regulation occurred simultaneously with TCR-zeta and ZAP-70 down-regulation in CD28+ lymphocytes. Actually, TCR-zetabright cell percentages progressively decrease passing from CD28bright to CD28int lymphocytes, and from CD28int to CD28dim lymphocytes, both in SF and PB. However, whereas SF CD28null lymphocytes further showed lower TCR-zetabright cell percentages compared to CD28dim lymphocytes (32.8±27.9 vs 38.9±28.6%, p 0.002), PB CD28null showed higher TCR-zetabright cell percentages compared to CD28dim (22.4±23.5 vs 17.1±23.4%, p 0.08) and similar to those in CD28int; conversely, PB CD28null showed lower percentages of lymphocytes expressing low TCR-zeta levels (TCR-zetadim) compared to CD28dim (4.8±6.3 vs 13.4±15.7%, p 0.001) and similar to those in CD28bright (Figure 1). Similar data derived from studying ZAP-70 levels in relation to CD28 expression. Conclusion: T CD28nullTCR-zetaint lymphocyte subsets significantly correlated with disease activity in arthritis patients. In SF, but not in PB, CD28 loss occurs in parallel with progressive TCR-zeta and ZAP-70 down-regulation; this suggests that CD28null lymphocytes in SF may be a sequel of chronic inflammatory stimulation, whereas PB CD28null lymphocyte origins are probably more complex, being conditioned by aging, sexual factors, cardiovascular comorbidities.
Different levels of TCR-zeta chain and ZAP-70 characterize distinct subsets of T CD28null lymphocytes in arthritis patients
Gremese E;
2010-01-01
Abstract
Background: The role and the origins of T CD28null lymphocytes in arthritis are still somewhat controversial. Objectives: To correlate TCR-zeta chain and ZAP-70 levels to CD28 expression in T lymphocytes of arthritis patients. Methods: We studied by flow cytometry CD28, TCR-zeta and ZAP-70 expression in T lymphocytes from peripheral blood (PB) and synovial fluid (SF) of 25 arthritis patients (16 RA, 5 PsA, 4 microcrystal arthritis; M/F:14/11; mean age 56.0±18.4). Results: PB CD8CD28null lymphocytes were more abundant than in SF (27.6±1 vs 41±23.3%; p 0.009), and higher in females (32.9±21.7 vs 53.5±20.9%; p 0.04). Both PB CD4CD28null and CD8CD28null were more frequent in those with cardiovascular comorbidities (21±15.4 vs 7.0±5.2%, p 0.003, and 60.6±17.5 vs 34±21.3%, p 0.02, respectively). Both PB CD8CD28null and CD4 CD8CD28null directly correlated with ESR (p 0.01, r +0.55, and p 0.002, r +0.66, respectively) and age (p 0.03, r +0.45, and p 0.07, r +0.40, respectively). Although PB total CD28null lymphocytes seemed not to be related to acute joint inflammation, the percentages of cells expressing intermediate TCR-zeta levels among CD4CD28null and CD8CD28null lymphocytes (CD28nullTCR-zetaint), both in PB and SF, directly correlated with arthritis activity (ESR, CRP, SF leukocyte count and neutrophil percentage, swollen joint count, DAS44 in RA patients). Instead, CD28null lymphocytes expressing high TCR-zeta levels (CD28nullTCR-zetabright) inversely correlated with activity indices. Finally, we observed that CD28 down-regulation occurred simultaneously with TCR-zeta and ZAP-70 down-regulation in CD28+ lymphocytes. Actually, TCR-zetabright cell percentages progressively decrease passing from CD28bright to CD28int lymphocytes, and from CD28int to CD28dim lymphocytes, both in SF and PB. However, whereas SF CD28null lymphocytes further showed lower TCR-zetabright cell percentages compared to CD28dim lymphocytes (32.8±27.9 vs 38.9±28.6%, p 0.002), PB CD28null showed higher TCR-zetabright cell percentages compared to CD28dim (22.4±23.5 vs 17.1±23.4%, p 0.08) and similar to those in CD28int; conversely, PB CD28null showed lower percentages of lymphocytes expressing low TCR-zeta levels (TCR-zetadim) compared to CD28dim (4.8±6.3 vs 13.4±15.7%, p 0.001) and similar to those in CD28bright (Figure 1). Similar data derived from studying ZAP-70 levels in relation to CD28 expression. Conclusion: T CD28nullTCR-zetaint lymphocyte subsets significantly correlated with disease activity in arthritis patients. In SF, but not in PB, CD28 loss occurs in parallel with progressive TCR-zeta and ZAP-70 down-regulation; this suggests that CD28null lymphocytes in SF may be a sequel of chronic inflammatory stimulation, whereas PB CD28null lymphocyte origins are probably more complex, being conditioned by aging, sexual factors, cardiovascular comorbidities.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
