Abstract
The role of the thymus in immune reconstitution in adults receiving chemotherapy is controversial. Detection of T-cell-receptor gene rearrangement excisional circles (TREC) in peripheral blood T cells has been shown to estimate thymic output. Therefore, we measured TREC levels to assess the contribution of the thymus to immune recovery following treatment with fludarabine. Patients who had received fludarabine alone or a fludarabine containing regimen were identified. Cryopreserved peripheral-blood mononuclear cells were obtained and analyzed by four-color flow cytometry utilizing fluorochrome-conjugated antibodies against CD4, CD8, CD45RO and CD27. Proportions of naïve T cells in each CD4+ and CD8+ subset were measured by gating on CD45RO-negative, CD27+ cells. Quantification of TREC in sorted naïve CD4+ and CD8+ T cells was performed by real-time PCR. Thirteen patients received a mean of 3.8 ± 0.4 courses of fludarabine and samples were obtained at a average of 18.8 (range 3.6-40.3) months after completing chemotherapy. Ten (77%) had detectable TREC levels. There was a positive correlation (Spearman's rank correlation) between the degree of TREC expression and the percentage of naïve T cells (r = 0.6, p = 0.03), naïve CD4+ (r = 0.6, p = 0.03) and naïve CD8+ (r = 0.66, p = 0.01) cells. We conclude that increased thymic output as demonstrated by an increase in TREC levels correlated with, and was predictive of, increased numbers of naïve T cell following fludarabine administration. The thymus appears to play a role in immune recovery in adults after receiving chemotherapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 343-348 |
| Number of pages | 6 |
| Journal | Leukemia and Lymphoma |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2003 |
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Keywords
- Fludarabine therapy
- Four-color flow cytometry
- T cell receptor gen rearragment excisional circles
- Thymic output
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Evaluation of thymic output by measurement of T-cell-receptor gene rearrangement excisional circles (TREC) in patients who have received fludarabine. / Aquino, Victor M.; Douek, Daniel C.; Berryman, Brian; Johnson, Matthew; Jain, Vinay K.; Collins, Robert H.
In: Leukemia and Lymphoma, Vol. 44, No. 2, 01.02.2003, p. 343-348.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evaluation of thymic output by measurement of T-cell-receptor gene rearrangement excisional circles (TREC) in patients who have received fludarabine
AU - Aquino, Victor M.
AU - Douek, Daniel C.
AU - Berryman, Brian
AU - Johnson, Matthew
AU - Jain, Vinay K.
AU - Collins, Robert H.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - The role of the thymus in immune reconstitution in adults receiving chemotherapy is controversial. Detection of T-cell-receptor gene rearrangement excisional circles (TREC) in peripheral blood T cells has been shown to estimate thymic output. Therefore, we measured TREC levels to assess the contribution of the thymus to immune recovery following treatment with fludarabine. Patients who had received fludarabine alone or a fludarabine containing regimen were identified. Cryopreserved peripheral-blood mononuclear cells were obtained and analyzed by four-color flow cytometry utilizing fluorochrome-conjugated antibodies against CD4, CD8, CD45RO and CD27. Proportions of naïve T cells in each CD4+ and CD8+ subset were measured by gating on CD45RO-negative, CD27+ cells. Quantification of TREC in sorted naïve CD4+ and CD8+ T cells was performed by real-time PCR. Thirteen patients received a mean of 3.8 ± 0.4 courses of fludarabine and samples were obtained at a average of 18.8 (range 3.6-40.3) months after completing chemotherapy. Ten (77%) had detectable TREC levels. There was a positive correlation (Spearman's rank correlation) between the degree of TREC expression and the percentage of naïve T cells (r = 0.6, p = 0.03), naïve CD4+ (r = 0.6, p = 0.03) and naïve CD8+ (r = 0.66, p = 0.01) cells. We conclude that increased thymic output as demonstrated by an increase in TREC levels correlated with, and was predictive of, increased numbers of naïve T cell following fludarabine administration. The thymus appears to play a role in immune recovery in adults after receiving chemotherapy.
AB - The role of the thymus in immune reconstitution in adults receiving chemotherapy is controversial. Detection of T-cell-receptor gene rearrangement excisional circles (TREC) in peripheral blood T cells has been shown to estimate thymic output. Therefore, we measured TREC levels to assess the contribution of the thymus to immune recovery following treatment with fludarabine. Patients who had received fludarabine alone or a fludarabine containing regimen were identified. Cryopreserved peripheral-blood mononuclear cells were obtained and analyzed by four-color flow cytometry utilizing fluorochrome-conjugated antibodies against CD4, CD8, CD45RO and CD27. Proportions of naïve T cells in each CD4+ and CD8+ subset were measured by gating on CD45RO-negative, CD27+ cells. Quantification of TREC in sorted naïve CD4+ and CD8+ T cells was performed by real-time PCR. Thirteen patients received a mean of 3.8 ± 0.4 courses of fludarabine and samples were obtained at a average of 18.8 (range 3.6-40.3) months after completing chemotherapy. Ten (77%) had detectable TREC levels. There was a positive correlation (Spearman's rank correlation) between the degree of TREC expression and the percentage of naïve T cells (r = 0.6, p = 0.03), naïve CD4+ (r = 0.6, p = 0.03) and naïve CD8+ (r = 0.66, p = 0.01) cells. We conclude that increased thymic output as demonstrated by an increase in TREC levels correlated with, and was predictive of, increased numbers of naïve T cell following fludarabine administration. The thymus appears to play a role in immune recovery in adults after receiving chemotherapy.
KW - Fludarabine therapy
KW - Four-color flow cytometry
KW - T cell receptor gen rearragment excisional circles
KW - Thymic output
UR - http://www.scopus.com/inward/record.url?scp=0037300571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037300571&partnerID=8YFLogxK
U2 - 10.1080/1042819021000029696
DO - 10.1080/1042819021000029696
M3 - Article
C2 - 12688355
AN - SCOPUS:0037300571
VL - 44
SP - 343
EP - 348
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 2
ER -