title: T-cell effector function and unresponsiveness in the murine lymphocytic choriomeningitis virus infection. II. Delayed-type hypersensitivity unresponsiveness reflects a defective differentiation from TD precursor to effector cell.
abstract: An increase in the virus dose from 10(2) LD50 (low dose) to 10(4) LD50 (high dose) of lymphocytic choriomeningitis virus (LCMV) results in markedly delayed virus clearance, in spite of a potent cytotoxic T-cell (TC) response. However, virus-specific delayed-type hypersensitivity (DTH) reactivity is markedly depressed in high-dose mice, suggesting an association between DTH and virus clearance. When virus-primed memory cells are transferred, DTH reactivity as well as virus-clearing capacity is restored in high-dose mice, indicating that the virus is not present in a changed or concealed form. The role of T-cells mediating DTH (TD cells) in virus clearance was also studied by adoptive transfer to naive recipients. Here the high-dose primed cells did mediate virus clearance, although no DTH reaction was detectable 24-72 h after transfer. However, when footpad swelling was measured 96 h or more after transfer a DTH response emerged, indicating that TD priming had taken place in high-dose animals. Pre-irradiation of high-dose primed cells markedly inhibited the antiviral activity as well as DTH, suggesting that upon transfer to naive recipients TD precursors from high-dose mice would proliferate into effector cells capable of mediating both functions. Treatment with anti-Lyt2+C' abrogated the capacity to induce virus-specific DTH, thus confirming that the cells involved are not helper T (TH) cells. We conclude that the DTH unresponsiveness in high-dose mice reflects a defective differentiation of TD precursor into effector cells which is reversible upon transfer to a less antigen loaded environment. Furthermore, it is suggested that TD function is crucial to the process of virus clearance.
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000950:Antigens, Ly