Lymphokine-dependent proliferation of T-lymphoid cells: regulated responsiveness and role in vivo.
The discovery of lymphokines stemmed from their ability to promote T-lymphocyte proliferation in vitro. Even after 20 years of intensive investigation, crucial aspects remain to be clarified about the role of specific lymphokines in T-cell proliferation and the biochemical mechanisms by which they play these roles, particularly in vivo. The present review focuses on conventional populations of TCR(alpha)beta T cells. Older findings and new insights into the function of specific lymphokines in T-lymphocyte proliferation in vivo are summarized along with unanswered questions raised by these observations. Vital contributions of lymphokines to clonal proliferation arise from two processes: the protection of cells against apoptosis and the activation of cell cycling. Findings are underscored indicating that the activity of a particular lymphokine depends on the subset of T cells (CD4 vs. CD8; naive vs. memory) to which it binds, and that point to potential pitfalls of extrapolating from tissue culture-adapted models to the regulation of T cells in vivo. After summaries of signaling mechanisms related to the proliferative activity of lymphokines, recent findings are highlighted suggesting that such signaling is a regulated and plastic process rather than one fixed schema of action.
Boothby
M
M
Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232-2363, USA. mark.boothby@mcmail.vanderbilt.edu
Mora
A L
AL
Stephenson
L M
LM
D000818:Animals; D002455:Cell Division; D016298:Hematopoietic Cell Growth Factors / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008222:Lymphokines / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016298:Hematopoietic Cell Growth Factors; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D008024:Ligands; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D015847:Interleukin-4