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 Triminally differentiated, and levels of tumor‐specific serum antibodies are elevated. These results imply the presence of unique helper T(T_h) 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 prolifer‐ative responses of lymphocytes from draining lymph nodes and spleens. In addition, we examined the lymphokine secretion profiles [interleukin (IL) 2, IL4] 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 IL2 only, or IL2 plus IL4. In addition, IL2‐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 IL2 after antigen stimulation. However, no IL4‐secreting cells were found. According to a recent model of differentiation of CD4⁺ T cells, precursors of T_h cells (that secrete IL2 alone) differentiate into T_h0 cells that can secrete IL2, IL4 and IFN‐γ. These cells further differentiate into T_h1 cells and T_h2 cells that secrete IL2 or IL4, respectively. We interpret the absence of IL4‐secreting CD4⁺ cells in AC tumor bearing mice to mean that in these mice precursor T_h cells are unable/prevented from differentiating into T_h0 cells.