TY - JOUR
T1 - Use of interleukin-7, interleukin-2, and interferon-γ to propagate CD4+T cells in culture with maintained antigen specificity
AU - Cohen, Peter A.
AU - Kim, Hyun
AU - Fowler, Daniel H.
AU - Gress, Ronald E.
AU - Jakobsen, Michael K.
AU - Alexander, Richard B.
AU - Mulé, James J.
AU - Carter, Charles
AU - Rosenberg, Steven A.
PY - 1993/10
Y1 - 1993/10
N2 - In contrast to CD8+T cells, it has been difficult to establish consistently satisfactory conditions for the bulk culture of antitumor CD4+T cells in either mice or humans. This difficulty is not limited to tumor antigen, since similar problems are encountered growing CD4+T cells that recognize alloantigen, tetanus, or candida. Four basic findings are reviewed in this article, stemming from work with identical results in both human and mouse. (a) Although CD4+T cells initially proliferate after exposure to appropriate antigen-presenting cells (APCs), such proliferation is not sustained; however, expansion of CD4+T cells can be achieved with the addition of recombinant interleukin-2 (rIL2) or rIL-7. (b) Specific CD4+responses to antigens are often better sustained with exogenous IL-7 than with exogenous IL-2. (c) Adding rIL-7 or rIL-2 permits sustained CD4+T-cell proliferation, but subsequent culture restimulation is complicated by high background reactivity to APCs whether APCs are antigen pulsed or not; this problem can be overcome by addition of exogenous interferon-γ (IFN-γ) to the CD4+cultures. (d) In certain instances proliferation is paradoxically impaired by reexposure to specific antigen, possibly reflecting apoptosis; this problem is also overcome by addition of rINF-γ to culture. We conclude that combinations of exogenous IL-7, IL-2, and IFN-γ with APC restimulation can be used to sustain antigen-specific CD4+T cells in culture. Using these techniques, antitumor CD4+T cells were propagated from the peripheral blood of two tumor-bearing patients.
AB - In contrast to CD8+T cells, it has been difficult to establish consistently satisfactory conditions for the bulk culture of antitumor CD4+T cells in either mice or humans. This difficulty is not limited to tumor antigen, since similar problems are encountered growing CD4+T cells that recognize alloantigen, tetanus, or candida. Four basic findings are reviewed in this article, stemming from work with identical results in both human and mouse. (a) Although CD4+T cells initially proliferate after exposure to appropriate antigen-presenting cells (APCs), such proliferation is not sustained; however, expansion of CD4+T cells can be achieved with the addition of recombinant interleukin-2 (rIL2) or rIL-7. (b) Specific CD4+responses to antigens are often better sustained with exogenous IL-7 than with exogenous IL-2. (c) Adding rIL-7 or rIL-2 permits sustained CD4+T-cell proliferation, but subsequent culture restimulation is complicated by high background reactivity to APCs whether APCs are antigen pulsed or not; this problem can be overcome by addition of exogenous interferon-γ (IFN-γ) to the CD4+cultures. (d) In certain instances proliferation is paradoxically impaired by reexposure to specific antigen, possibly reflecting apoptosis; this problem is also overcome by addition of rINF-γ to culture. We conclude that combinations of exogenous IL-7, IL-2, and IFN-γ with APC restimulation can be used to sustain antigen-specific CD4+T cells in culture. Using these techniques, antitumor CD4+T cells were propagated from the peripheral blood of two tumor-bearing patients.
KW - CD4T cells
KW - Dendritic cells
KW - Interferon-γ
KW - Interleukin-7
UR - http://www.scopus.com/inward/record.url?scp=0027494098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027494098&partnerID=8YFLogxK
U2 - 10.1097/00002371-199310000-00012
DO - 10.1097/00002371-199310000-00012
M3 - Article
C2 - 7507711
AN - SCOPUS:0027494098
VL - 14
JO - Journal of Biological Response Modifiers
JF - Journal of Biological Response Modifiers
SN - 1053-8550
IS - 3
ER -