Numerical depletion and functional deficiency of helper/inducer T-lymphocytes are universal findings in patients with AIDS. Numerous other immune abnormalities are also present in AIDS patients, and the specific role of the helper T-lymphocyte (HTL) in the host response to opportunistic infections observed in this population is unknown. Severe and prolonged herpes simplex virus infections are common in AIDS patients. If HTL deficiency is responsible for the severe manifestations of HSV infections observed in AIDS patients, then depletion of HTL's by an alternate mechanism should reproduce the increased susceptibility to HSV as well as the immune abnormalities observed in this patient population. We propose to evaluate the role of HTL's in host resistance to opportunistic infections, using central nervous system and cutaneous HSV infection in mice depleted on HTL's. Preliminary experiments have shown the surprising result that HTL depletion has little effect on neural HSV infection, despite abrogation of the humoral immune response and blunting of the cell mediated immune response. We propose to expand these observations, and to determine the mechanism of host resistance to HSV in HTL depleted mice.
Specific aims i n these experiments include: 1) to determine host defense mechanisms responsible for resistance to HSV encephalitis in HTL depleted mice, 2) to determine the role of HTL's in resistance to cutaneous HSV Infection, 3) to evaluate the role of HTL's in mediating resistance to reinfection with HSV following immunization, 4) to determine the effects of HTL depletion on the entire spectrum of cellular and humoral immune responses, and to determine whether infection during HTL depletion results in antigen tolerance. The investigations will provide definitive data on the role of the HTL in the host resistance to HSV infection, and will contribute to our understanding of the pathogenesis of opportunistic infections in AIDS.
| Murray, J F; Mills, J (1990) Pulmonary infectious complications of human immunodeficiency virus infection. Part I. Am Rev Respir Dis 141:1356-72 |
| Murray, J F; Mills, J (1990) Pulmonary infectious complications of human immunodeficiency virus infection. Part II. Am Rev Respir Dis 141:1582-98 |
