A factor from CD8 cells of human immunodeficiency virus-infected patients suppresses HLA self-restricted T helper cell responses

Defective in vitro T helper cell (T_h) function can occur in asymptomatic human immunodeficiency virus (HIV)-seropositive (HIV⁺) individuals. A characteristic, early finding is the loss of an in vitro response to recall antigens, such as influenza A virus (FLU), despite an intact T_h response to alloantigen (ALLO). To determine whether suppressor cells and/or inhibitory factors could contribute to this HIV-associated T_h immunodeficiency, coculture studies were performed using peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV-infected (HIV⁺) and one of whom was uninfected (HIV-seronegative, HIV^-). In vitro T_h function was measured as interleukin 2 production or proliferation to FLU and ALLO. Two pairs of twins were repetitively studied. A single HIV⁺ individual with multiple samples of cryopreserved PBLs over 6 years (including a HIV^- specimen) was also studied. PBLs from the HIV⁺, but not from the HIV^-, individuals demonstrated defective in vitro Th function in response to FLU but not to ALLO. PBLs from HTV⁺ individuals could induce a similar defect in the T_h function of syngeneic or autologous HIV^- PBLs. This suppression was generated by CD4-depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8⁺ cells of HIV⁺ donors was generated by 24-hr unstimulated cultures of HIV⁺ PBLs. This factor inhibited FLU but not ALLO responses of autologous, syngeneic, or allogeneic HIV^- PBLs. This suppressive effect could not be explained by HIV infection or replication during the culture period. These results demonstrate that selective abrogation of T_h function to recall antigens in HIV⁺ individuals is associated with an inhibitory factor produced by CD8⁺ T cells. (.