Non-MHC-restricted target-cell lysis by a CD4-CD8- TCR alpha beta T-cell line, as well as by TCR gamma delta T-cell lines, results from lymphokine-activated killing.
A long-term CD4-CD8- TCR alpha beta human T-cell line, as well as similar CD4-CD8- TCR gamma delta T-cell lines for comparison, were generated from various tissues by negative selection using anti-CD4 and anti-CD8 monoclonal antibodies (MAbs) followed by positive selection with specific anti-TCR MAb and then repeated in vitro stimulation with interleukin-enriched media and lectin. These cell lines all demonstrated non-MHC-restricted cytolysis on a variety of human tumor cell lines. However, removal of lymphokines from the culture media for 24 hr abrogated most of the non-MHC-restricted target-cell lysis without affecting TCR alpha beta or TCR gamma delta cell viability or TCR function as determined by antibody-triggered redirected target-cell lysis. Subsequent re-exposure to lymphokines reconstituted non-MHC-restricted cytolysis by these cell lines. Thus, much of the non-specific, non-MHC-restricted cytolytic activity generated by CD4-CD8- TCR alpha beta or TCR gamma delta cells is secondary to lymphokine-activated killing (LAK) activity. These cells have potent LAK activity and may be prominent in LAK-cell populations. In addition, after lymphokine deprivation, both CD4-CD8- TCR alpha beta and TCR gamma delta cells showed residual activity against some tumor-cell targets, the nature of which remains to be defined.
Maziarz
R T
RT
Division of Pediatric Oncology, Brigham and Women's Hospital, Boston, MA 02115.
Groh
V
V
Prendergast
M
M
Fabbi
M
M
Strominger
J L
JL
Burakoff
S J
SJ
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D009369:Neoplasms; D009374:Neoplasms, Experimental; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D008222:Lymphokines; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell