In vitro expansion of CD4+CD25highFOXP3+CD127low/− regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans

2007 ◽  
Vol 9 (11) ◽  
pp. 1325-1332 ◽  
Author(s):  
Jean-Michel Hougardy ◽  
Virginie Verscheure ◽  
Camille Locht ◽  
Françoise Mascart
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
In Vitro Expansion

scholarly journals Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2024-2029 ◽  
Author(s):  
NE Kay ◽  
N Bone ◽  
M Hupke ◽  
AP Dalmasso
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Adult Male ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Normal Adult ◽  
Cd8 Cells ◽  
Blood Lymphocytes

Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

scholarly journals Expansion of a lymphocyte population co-expressing T4 (CD4) and T8 (CD8) antigens in the peripheral blood of a normal adult male

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2024-2029 ◽  
Author(s):  
NE Kay ◽  
N Bone ◽  
M Hupke ◽  
AP Dalmasso
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Adult Male ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Normal Adult ◽  
Cd8 Cells ◽  
Blood Lymphocytes

Abstract Approximately 2% to 3% of circulating human T cells co-express CD4 and CD8 (CD4+, CD8+) T-cell antigens. These CD4+, CD8+ cells may be immature precursors that function to replenish functional T-cell subsets. We detected a very high level of CD4+, CD8+ cells in the peripheral blood lymphocytes of a healthy white male, ranging from 21% to 36%. The morphology of his peripheral blood lymphocytes was normal, and he has maintained an elevated level of CD4+, CD8+ cells without clinical disease over a 19-month observation period. The CD4+, CD8+ cells did not possess thymocyte membrane antigen (CD6), nor did they have increased Tac (CD25) antigen. His intact, purified blood T cells had a normal proliferative response to phytohemagglutinin and interleukin-2 (IL-2), provided help for B-cell proliferation at control levels and exposure to IL-2 resulted in generation of cytotoxic cells. However, the purified blood CD4+, CD8+ cells were deficient in these latter functions except for help in B-cell function. Despite defective function, the isolated CD4+, CD8+ cells co-expressed CD2 and CD3. Prolonged in vitro culture of CD4+, CD8+ cells was possible in the presence of recombinant IL-2. The cultured CD4+, CD8+ cells retained the double antigens (CD4 and CD8) throughout a 4-week period. It is likely these cells are less mature than CD4+, CD8- or CD4-, CD8+ T cells as the CD4+, CD8+ have less in vitro function than the former cells, but it is not yet clear if they mature into either CD4+, CD8-, or CD4-, CD8+ cells. Finally, the presence of an expanded, hypofunctioning CD4+, CD8+ cell population in a normal adult male is apparently compatible with excellent clinical health.

scholarly journals Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 404-411 ◽  
Author(s):  
S Buysmann ◽  
FJ Bemelman ◽  
PT Schellekens ◽  
Y van Kooyk ◽  
CG Figdor ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Lymphocytes ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Blood Lymphocytes

Abstract We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

scholarly journals Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 404-411 ◽  
Author(s):  
S Buysmann ◽  
FJ Bemelman ◽  
PT Schellekens ◽  
Y van Kooyk ◽  
CG Figdor ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Lymphocytes ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Blood Lymphocytes

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

Long-Term Follow-up of Patients with Recurrent Malignant Gliomas Treated with Adjuvant Adoptive Immunotherapy

Neurosurgery ◽  
1991 ◽  
Vol 28 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Kevin O. Lillehei ◽  
Dawn H. Mitchell ◽  
Stephen D. Johnson ◽  
Larry E. McCleary ◽  
Carol A. Kruse
Keyword(s):  
Survival Time ◽  
Adoptive Immunotherapy ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Lak Cells ◽  
Prior Chemotherapy ◽  
Blood Lymphocytes ◽  
Significant Difference

Abstract Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas. The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed. The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d. range, 0-32). The average number of lymphocytes implanted was 7.6 × 109 (range, 1.9-27.5 × 109), together with 1 to 4 × 106 U of rIL-2. To date, 10 of the 11 patients died, all from recurrent tumor growth. The median overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not. The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells. Prior chemotherapy did correlate, however, with diminished in vitro cytotoxicity against the natural killer-sensitive (K562) target cell by LAK cells (P < 0.05) but not that by ASL. There were no major adverse side effects. Although adoptive immunotherapy was safe and well tolerated, its therapeutic potential remains in question.

Sign in / Sign up

Export Citation Format

Share Document