The Acquired Immunodeficiency Syndrome (AIDS) is a disease found primarily in homosexual men consisting of opportunistic infections and tumors and is due to an acquired T-cell defect. The purpose of this research is to determine which T-cell functions might serve to distinguish homosexuals with a symptom complex including lymphadenopathy from those with AIDS. Our findings demonstrated that T lymphocytes from the lymphadenopathy and AIDS patients had markedly depressed proliferative responses in the autologous (auto)--and allogeneic (allo)--mixed lymphocyte reaction (MLR) compared to healthy homosexuals or heterosexual controls (p less than .001). Since proliferation in the MLR depends upon interleukin-2 (IL-2), a T-cell growth factor, we studied the production of, and response to, IL-2 in various groups of homosexuals and in heterosexual controls. IL-2 production was markedly depressed in the lymphadenopathy and AIDS patients, 1.0 U/ml and 0.1 U/ml, respectively, compared to the healthy homosexual or heterosexual controls, both 5 U/ml (p less than 0.05 and p less than 0.01, respectively). Although the autoMLR of the lymphadenopathy patients rose to control values with the addition of exogenous IL-2, the autoMLR of the AIDS patients did not (p less than .01). This lack of responsiveness to IL-2 in the AIDS group was due to their inability to generate IL-2 receptors as shown by the absence of IL-2 absorption by activated cells and the absence of the Tac antigen (IL-2 receptor) on these same cells. The T4?+? and T8?+? T-cell subsets from the AIDS patients each demonstrated depressed IL-2 production and responsiveness following activation with autologous cells or mitogen, as well as the absence of Tac antigen. The diminished T-cell proliferation in the autoMLR in the lymphadenopathy group is associated with one defect, low IL-2 production, while the depressed proliferation in the AIDS group is aasociated with two defects, low IL-2 production and lack of IL-2 receptor generation. These studies demonstrate that IL-2 receptor generation distinguishes homosexuals with lymphadenopathy from those with AIDS, and that in addition to T-cell defects in the OKT4?+? T-cell subset, there are significant abnormalities in the OKT8?+? T-cell subset in AIDS patients. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA034981-03
Application #
3548350
Study Section
(SSS)
Project Start
1983-09-30
Project End
1987-05-31
Budget Start
1985-09-01
Budget End
1987-05-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107