The role of I-region associated antigen (Ia)-bearing accessory cells in the generation of cytotoxic T cells in a subpopulation of thymocytes.

The roles of killer-helper factor (KHF) and accessory cells bearing I-region associated antigen (Ia) in the generation of cytotoxic T lymphocytes (CTL) were analyzed. Peanut agglutinin-binding (PNA+) thymocytes from C3H/HeN mice generated efficient CTL responses against 2,4,6-trinitrophenyl (TNP)-modified syngeneic spleen cells in the presence of cell-free supernatant (CFS) derived from purified protein derivatives (PPD)-stimulated Mycobacterium tuberculosis-primed BALB/c spleen cell culture (PPD-CFS). The KHF which is present in PPD-CFS devoid of the activities of IL-1 or IL-2 was required in conjunction with IL-2 for generation of CTL in PNA+ thymocytes. In contrast, PNA- thymocytes as well as spleen cells could generate CTL in the absence of helper factors. However, a significant CTL response against Ia-negative syngeneic tumor cells was not induced from either PNA+, PNA- thymocytes or spleen cells in the absence of Ia-positive accessory cells. Moreover, the treatment of spleen cells with relevant anti-Ia antiserum plus complement before TNP-modification abrogated the stimulatory capacity of TNP-spleen cells. In both cases, the addition of Ia-positive accessory cells restored the impaired capacity of TNP-modified stimulator cells. The addition of IL-1 to the culture of PNA- thymocytes or spleen cells stimulated with TNP-X5563 cells in the absence of accessory cells restored the CTL generation. In contrast, the addition of IL-1 to the culture of PNA+ thymocytes was ineffective. The role of Ia-positive accessory cells in the generation of CTL in a subpopulation of thymocytes is discussed.