Characterization of specific T helper cell activity in mice bearing alloantigenic tumors in the anterior chamber of the eye

Abstract

P815 tumor cells injected in the anterior chamber (AC) of eyes of BALB/c mice elicit anterior chamber-associated immune deviation (ACAID) whereby delayed-type hypersensitivity (DTH) responses to the tumor-associated antigens are suppressed, precursors of cytotoxic T cells are clonally expanded but not terminally differentiated, and levels of tumor-specific serum antibodies are elevated. These results imply the presence of unique helper T (Th) cell functions in these animals. To identify and describe these cells, we first determined the presence of antigen-activated lymphocytes in AC tumor-bearing mice, as well as mice that received tumor cells subconjunctivally (SC), as measured by proliferative responses of lymphocytes from draining lymph nodes and spleens. In addition, we examined the lymphokine secretion profiles [interleukin (IL) 2, IL 4] of antigen-responsive lymph node and spleen cells in limiting dilution analysis. We found that lymphoid organs of mice primed by the SC route contained high frequencies of antigen-reactive CD4+ cells that secreted IL 2 only, or IL 2 plus IL 4. In addition, IL 2-secreting CD8+ cells were found. Alternatively, the lymphoid organs of mice receiving AC inoculations of P815 cells contained CD4+ as well as CD8+ cells that secreted IL 2 after antigen stimulation. However, no IL 4-secreting cells were found. According to a recent model of differentiation of CD4+ T cells, precursors of Th cells (that secrete IL 2 alone) differentiate into Th0 cells that can secrete IL 2, IL 4 and IFN-gamma. These cells further differentiate into Th1 cells and Th2 cells that secrete IL 2 or IL 4, respectively. We interpret the absence of IL 4-secreting CD4+ cells in AC tumor bearing mice to mean that in these mice precursor Th cells are unable/prevented from differentiating into Th0 cells.