1. Anti suppression T cells (TAS). T cell differentiation factor (TCDF) induced the generation of TAS in allogeneic mixed lymphocyte culture. TAS specifically abrogated the suppressive effect of TS (suppression T cells) which suppress CTL activity. Generation of TAS was dependent on CD4 and Thy 1 molecules but was not affected by antibodies against CD8 or class II MHC determinants, and thus TAS were different from contra suppressor cells or T helper cells. TAS may represent a new class of immunoregulatory cells that regulate the cytotoxic activity of CTL. 2. Asialo GM1 as an accessory molecule for CTL - mediated cytotoxicity. The blocking by alpha ASGM1 was largely dependent on the expression of ASGM1 on effector cells. Furthermore, all ASGM1+ CTL exerted different degrees of NK- or LAK-like cytotoxicity, whereas the ASGM1- CTL displayed more restricted specificity against appropriate targets. Hence, the expression of ASGM1 on CTL determines both the specificity and the cytotoxic activity of the cytotoxic reactions. 3. Effect of alpha CD3 on lymphokine-activated killer cell activity. Antibody against the epsilon chain of T3 complex on T cells (alpha CD3) could augment the effector function of the cytotoxic activity of LAK cells, and could induce the generation of killer cells (CD3-AK) through the triggering of endogenous production of lymphokines by alpha CD3. The cytotoxic activity of the alpha CD3-induced killer cells (CD3-AK) generally paralleled that of the conventional LAK cells. In contrast to LAK cells which only survived in culture for 6-10 days, the CD3-AK cells could be maintained in vitro in active growth for 3-5 weeks with high levels of anti-tumor cytotoxic activity. Thus the CD3-AK may be an ideal candidate for use in adjuvant adoptive immunotherapy of cancer.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009272-06
Application #
3916417
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code