Previous studies have shown that depletion of CD8(+) cells during acute and chronic simian immunodeficiency virus (SIV) infection leads to increased viral replication, morbidity, and mortality, which have been attributed to loss of CD8(+) T cell-mediated control of SIV. However, these studies did not exclude that CD8(+) cell depletion increased homeostatic proliferation of CD4(+) T cells, resul...

We here describe novel aspects of CD8(+) and CD4(+) T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8(+) T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8(+) T cells and their differentiation of effector functions is limited, but both dramatica...

Recent high throughput sequencing analysis has revealed that the TCRβ repertoire is largely different between CD8(+) and CD4(+) T cells. Here, we show that the transduction of SIG35α, the public chain-centric HLA-A*02:01(A2)/MART127-35 TCRα hemichain, conferred A2/MART127-35 reactivity to a substantial subset of both CD8(+) and CD4(+) T cells regardless of their HLA-A2 positivity. T cells indiv...

Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8(+) T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4(...

The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n = 42), thos...

The role of CD4+ T cells in promoting CD8+ T cell effector activity in response to transplant Ags in vivo has not been reported. We used a hepatocellular allograft model known to initiate both CD4-dependent and CD4-independent rejection responses to investigate the contribution of CD4+ T cells to the development, function, and persistence of allospecific CD8+ T cell effectors in vivo. Complete ...

We previously showed that HIV infection leads to expansion of a rapidly proliferating pool (s(1)) of CD4 and CD8 T lymphocytes. In the current study, we used in vivo labeling with bromodeoxyuridine to characterize the kinetics of naive, memory, and activated (HLA-DR(+)/CD38(+)) subpopulations of CD4 and CD8 T lymphocytes, and to examine the relationship between kinetic parameters and baseline C...

We have previously demonstrated that immunotherapy combining agonistic anti-CD40 and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of highly cytolytic, antigen-independent "bystander-activated" (CD8(+)CD44high) T cells displaying a CD25(-)NKG2D(+) phenotype in a cytokine dependent manner, which were responsible for the anti-tumor effects. While much attention has foc...

The magnitude and duration of CD8(+) T cell-mediated responses in the skin to hapten sensitization and challenge, contact hypersensitivity (CHS), is negatively regulated by CD4(+) T cells through an unknown mechanism. In this study we show that CD4(+) T cells restrict the development and expansion of hapten-specific CD8(+) T cells mediating CHS responses to 2,4-dinitrofluorobenzene. In the abse...

CD4 can be up-regulated on CD8+ T cells generating a CD4dimCD8bright phenotype. We previously demonstrated that the CD4dimCD8bright phenotype constitutes an activated phenotype of CD8+ T cells. We demonstrate here that the activated CD4dimCD8bright T cells are not undergoing apoptosis and do not produce significant intracellular levels of interferon gamma (IFNgamma), interleukin 2 (IL-2), or IL...