Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection
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Thjon J. Tang, Jaap Kwekkeboom, , Shanta Mancham, Rekha S. Binda, Robert A. de Man, Solko W. Schalm, Johannes G. Kusters and Harry L.A. Janssen
Department of Gastroenterology and Hepatology, Erasmus MC—University Medical Center Rotterdam, Room L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Received 30 August 2004; revised 17 January 2005; accepted 26 January 2005. Available online 25 April 2005.
Background/Aims
To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-α therapy of chronic HBV-patients using the FNAB technique.
Methods
Twenty chronic HBeAg+-patients were treated with pegylated α-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNγ and granzyme B (GrB) were immunocytochemically quantified.
Results
The relative numbers of CD56+ cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8+GrB+ lymphocytes, a small elevation in CD8+IFNγ+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy.
Conclusions
The intrahepatic CD8+ T-lymphocyte, but not the CD4+ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-α therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.
Decreased ratio of CD4/CD8 lymphocytes might be predictive for successful interferon alpha and lamivudine
This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.
http://www.ncbi.nlm.nih.gov/pubmed/12753145
entecavir effect on cd counts of hbeag positive
cd4/cd8 increase
cd4 increase
cd8 decrease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570678/
there is very little online, i d be interested to see if superhi cd8 has a meaning since they are not common on cronic hbv
Some Chinese patients on Interferon get reports on their CD+ counts. But I am not sure how they use the results. The Chinese doctors and hospitals provide all sorts of tests as a means to charge patients, even when the tests inform them nothing They also like to use medications to lower the ALT and extended courses of Interferon treatment - all just to make money.
found this study, but i dont have similar results, my total linfo count is high, cd8 is more than double, cd3 is also double, cd4/cd8 ratio is very low.....have no idea if this is meaningful
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092870/
table 2
Counts and proportions of patient peripheral lymphocyte subsets
T subsets CHB patients (n = 35) HBV carriers (n = 25) Healthy controls (n = 35)
White blood cells × 109/L 4.96 ± 1.18b 5.60 ± 0.96b 6.53 ± 1.42
Lymphocytes × 109/L (%) 1.60 ± 0.51b (32.7 ± 8.7) 1.72 ± 0.44b (31.2 ± 8.8) 2.13 ± 0.49 (33.1 ± 6.6)
Natural killer cells /μL (%) 197 ± 102a (12.2 ± 5.1) 272 ± 189 (15.1 ± 8.4) 310 ± 181 (14.6 ± 7.8)
B cells/μL (%) 228 ± 148 (14.3 ± 6.3) 220 ± 113 (12.6 ± 4.6) 242 ± 95 (11.4 ± 3.8)
CD3+ T cells/μL (%) 1145 ± 380b (71.5 ± 7.1) 1190 ± 278b (70.4 ± 9.6) 1516 ± 382 (71.4 ± 7.6)
CD3+CD4+ T cells/μL (%) 573 ± 194b (36.3 ± 6.9) 673 ± 148b (40.1 ± 6.9) 816 ± 259 (38.2 ± 7.0)
CD3+CD8+ T cells/μL (%) 489 ± 213a (30.1 ± 8.0) 445 ± 157b (25.9 ± 6.1) 609 ± 177 (28.9 ± 5.7)
CD4+/CD8+ 1.35 ± 0.62 1.64 ± 0.50 1.39 ± 0.44
CD8+CD38+ T cells/μL (%) 301 ± 152 (62.0 ± 14.7bd) 285 ± 121 (51.8 ± 18.5) 274 ± 81 (46.3 ± 11.9)
CD4+CD28+ T cells/μL (%1) 532 ± 191b (96.0) 622 ± 149a (95.7) 744 ± 221 (94.7)
CD8+CD28+ T cells/μL (%) 235 ± 125a (51.1 ± 15.5) 245 ± 100a (55.7 ± 16.0) 306 ± 94 (51.3 ± 11.7)
1Medians were used as the CD4+CD28+ T cell proportions were non-normal variables according to Kolmogorov-Smirnov Normality Test.
aP < 0.05,
bP < 0.01 vs normal healthy controls;
dP < 0.01 vs hepatitis B virus (HBV) carriers. CHB: Chronic hepatitis B.
of course consider that this might mean nothing because although cd8 count is high it can be impaired in the liver by hbsag making cd8 suidice or non responding to hbv
in any case i am curious to see their changes during gcmaf and the frequency in other cronic hbv patients