Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus-1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of CD8+ lymphocytes during primary SIV infection. Eliminating CD8+ lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8+ T cells. These results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.

To examine the role of T cell receptor (TCR) in gammadelta T cells in adaptive immunity, a macaque model was used to follow Vgamma2Vdelta2+ T cell responses to mycobacterial infections. These phosphoantigen-specific gammadelta T cells displayed major expansion during Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection and a clear memory-type response after BCG reinfection. Primary and recall expansions of Vgamma2Vdelta2+ T cells were also seen during Mycobacterium tuberculosis infection of naive and BCG-vaccinated macaques, respectively. This capacity to rapidly expand coincided with a clearance of BCG bacteremia and immunity to fatal tuberculosis in BCG-vaccinated macaques. Thus, Vgamma2Vdelta2+ T cells may contribute to adaptive immunity to mycobacterial infections.

Nonhuman primates provide valuable animal models for human diseases. However , studies assessing the role of cell-mediated immune responses have been difficult to perform in nonhuman primates. We have shown that CD8؉ lymphocyte-mediated immunity in rhesus monkeys can be selectively eliminated using the mouse-human chimeric anti-CD8 monoclonal antibody cM-T807. In vitro, this antibody completely blocked antigen-specific expansion of cytotoxic T cells and decreased major histocompatibility complex class I-restricted , antigen-specific lysis of target cells but did not mediate complement-dependent cell lysis. In vivo administration of cM-T807 in rhesus monkeys resulted in near total depletion of CD8؉ T cells from the blood and lymph nodes for up to 6 weeks. This depletion was not solely complementdependent and persisted longer in adults than in ju- Defining the role of the cellular and humoral components of the immune response to pathogens has furthered our understanding of the pathophysiology of various infectious diseases. Knowledge of these immune responses has also been valuable in designing immunization and other prophylactic strategies to prevent infection by these organisms. Animal models that permit passive administration of immunoglobulins or adoptive transfer of lymphocytes to naive hosts have been crucial for demonstrating the contribution of specific components of the immune response in controlling certain infections.Numerous experimental approaches have been used to study the role of CD8ϩ cell-mediated immunity in the control of infections. Studies demonstrating the importance of cellular immunity in various viral infections have been performed by adoptive transfer of lymphocytes in syngeneic mice. 1,2 Genetic knockout mice in which the CD8 or ␤ 2 microglobulin genes have been disrupted have been useful for defining the immunopathogenic role of cytotoxic T lymphocytes (CTL) in specific infectious agents. 3,4 Finally, rodents depleted of CD8ϩ lymphocytes by administration of CD8-specific monoclonal antibodies have been useful in determining the role of CTL in controlling pathogens.