Selective Defects in Cytomegalovirus- and Mitogen-Induced Lymphocyte Proliferation and Interferon Release in Patients with Acquired Immunodeficiency Syndrome

Abstract

To examine the defect in cellular immunity in patients with acquired immunodeficiency syndrome (AIDS), we studied in vitro lymphocyte proliferation and interferon (IFN) release in response to cytomegalovirus (CMV) antigen and Concanavalin A mitogen in 40 homosexual men with AIDS, 10 homosexual men with chronic lymphadenopathy syndrome, 7 healthy homosexual men, and 18 healthy heterosexual subjects of either sex. CMV serology by an enzyme-linked immunosorbent assay and viral cultures for CMV were performed. Lymphocytes of patients with AIDS showed impaired CMV-specific release of IFN but normal mitogen-induced IFN release. The defect was not attributable to CMV infection per se. Cell proliferation in response to both CMV antigen and mitogen was impaired in patients with AIDS who had opportunistic infections. The defect could not be attributed to CMV viremia. We concluded that impaired release of IFN in response to a viral antigen is characteristic of lymphocytes in patients with AIDS and that this defect is distinct from a defect in mitogenic responsiveness, which coexists predominantly in patients with opportunistic infections.

Global Dysfunction of CD4 T-Lymphocyte Cytokine Expression in Simian-Human Immunodeficiency Virus/SIV-Infected Monkeys Is Prevented by Vaccination

“…A reduction in the proliferative capacity of CD4 ϩ T lymphocytes in response to HIV antigens has been demonstrated (9,15,18,19,23,24). HIV type 1 (HIV-1) replication also inhibits antigen-specific CD4 ϩ T-lymphocyte progression through the cell division cycle (26).…”

“…HIV type 1 (HIV-1) replication also inhibits antigen-specific CD4 ϩ T-lymphocyte progression through the cell division cycle (26). Finally, a loss of the CD4 ϩ T lymphocytes' ability to secrete cytokines in response to viral antigen stimulation has been described in infected individuals (9,17). Since activated CD4 ϩ T cells are infected and destroyed by HIV-1, these sequelae of infection are not surprising (8,27).…”

Human Immunodeficiency Virus Type 1 Envelope Epitope-Specific CD4+T Lymphocytes in Simian/Human Immunodeficiency Virus-Infected and Vaccinated Rhesus Monkeys Detected Using a Peptide-Major Histocompatibility Complex Class II Tetramer

“…It has long been appreciated that HIV-1 infection is associated clinically with a gradual decline in CD4 ϩ T-lymphocyte numbers and an impairment of CD4 ϩ T-lymphocyte function (3,12,20). Recent studies have shown that control of viral replication in vivo is associated with vigorous HIV-1-specific CD4 ϩ T-lymphocyte proliferative responses (28).…”

“…Interpreting studies of CD4 ϩ T-lymphocyte responses elicited by an AIDS virus infection can, however, prove problematic. An AIDS virus infection, by virtue of the capacity of the virus to lyse and cause functional abnormalities of CD4 ϩ T cells, is associated with a very-low-frequency, dysfunctional CD4 ϩ T-lymphocyte response (3,12,20). We therefore chose to study the responses of CD4 ϩ T lymphocytes to AIDS viruses that are nonpathogenic and other AIDS viruses that are pathogenic but do not cause profound CD4-cell depletion (5,6,25,26).…”

Immune predispositions for cytomegalovirus retinitis in AIDS. The HNRC Group.

“…In addition, it is known that for CMV, CD8 as well as CD4 T cells proliferate when cultured with CMV infected cells (as antigen) (9, 10). In those immunosuppressed by HIV, Wahren et al (1987) and others (I1, 12,13) found that, on average, T cells from HIV (and CMV) infected donors had lower levels of T cell proliferation to CMV antigen in vitro than did cells from CMV-infected, HIV seronegative controls. However, within these average lower responses, there is considerable individual variation.…”