Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (K(b−/−)xD(b−/−) mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β(2)-microglobulin (β(2)-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β(2)-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β(2)-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells

Correlation functions in super Liouville theory

We calculate three- and four-point functions in super Liouville theory coupled to super Coulomb gas on world sheets with spherical topology. We first integrate over the zero mode and assume that a parameter takes an integer value. After calculating the amplitudes, we formally continue the parameter to an arbitrary real number. Remarkably the result is completely parallel to the bosonic case, the amplitudes being of the same form as those of the bosonic case.Comment: 11 page

Classical transport equation in non-commutative QED at high temperature

We show that the high temperature behavior of non-commutative QED may be simply obtained from Boltzmann transport equations for classical particles. The transport equation for the charge neutral particle is shown to be characteristically different from that for the charged particle. These equations correctly generate, for arbitrary values of the non-commutative parameter theta, the leading, gauge independent hard thermal loops, arising from the fermion and the gauge sectors. We briefly discuss the generating functional of hard thermal amplitudes.Comment: 11 page

A Note on Background (In)dependence

In general quantum systems there are two kinds of spacetime modes, those that fluctuate and those that do not. Fluctuating modes have normalizable wavefunctions. In the context of 2D gravity and ``non-critical'' string theory these are called macroscopic states. The theory is independent of the initial Euclidean background values of these modes. Non-fluctuating modes have non-normalizable wavefunctions and correspond to microscopic states. The theory depends on the background value of these non-fluctuating modes, at least to all orders in perturbation theory. They are superselection parameters and should not be minimized over. Such superselection parameters are well known in field theory. Examples in string theory include the couplings $t_k$ (including the cosmological constant) in the matrix models and the mass of the two-dimensional Euclidean black hole. We use our analysis to argue for the finiteness of the string perturbation expansion around these backgrounds.Comment: 16 page

Transport equation for the photon Wigner operator in non-commutative QED

We derive an exact quantum equation of motion for the photon Wigner operator in non-commutative QED, which is gauge covariant. In the classical approximation, this reduces to a simple transport equation which describes the hard thermal effects in this theory. As an example of the effectiveness of this method we show that, to leading order, this equation generates in a direct way the Green amplitudes calculated perturbatively in quantum field theory at high temperature.Comment: 13 pages, twocolumn revtex4 styl

Human cellular restriction factors that target HIV-1 replication

Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5α), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions

An Optimized CD4 T-Cell Response Can Control Productive and Latent Gammaherpesvirus Infection

CD4 T cells are important for control of infection with murine gammaherpesvirus 68 (γHV68), but it is not known whether CD4 T cells function via provision of help to other lymphocyte subsets, such as B cells and CD8 T cells, or have an independent antiviral function. Moreover, under conditions of natural infection, the CD4 T-cell response is not sufficient to eliminate infection. To determine the functional capacities of CD4 T cells under optimal or near-optimal conditions and to determine whether CD4 T cells can control γHV68 infection in the absence of CD8 T cells or B cells, we studied the effect of ovalbumin (OVA)-specific CD4 T cells on infection with a recombinant γHV68 that expresses OVA. OVA-specific CD4 T cells limited acute γHV68 replication and prolonged the life of infected T-cell receptor-transgenic RAG (DO.11.10/RAG) mice, demonstrating CD4 T-cell antiviral activity, independent of CD8 T cells and B cells. Despite CD4 T-cell-mediated control of acute infection, latent infection was established in DO.11.10/RAG mice. However, OVA-specific CD4 T cells reduced the frequency of latently infected cells both early (16 days postinfection) and late (42 days postinfection) after infection of mice containing CD8 T cells and B cells (DO.11.10 mice). These results show that OVA-specific CD4 T cells have B-cell and CD8 T-cell-independent antiviral functions in the control of acute infection and can, in the absence of preexisting CD8 T-cell or B-cell immunity, inhibit the establishment of gammaherpesvirus latency

An Optimized CD8(+) T-Cell Response Controls Productive and Latent Gammaherpesvirus Infection

Strategies to prime CD8(+) T cells against Murine gammaherpesvirus 68 (γHV68; MHV68) latency have, to date, resulted in only limited effects. While early forms of latency (<21 days) were significantly reduced, effects were not seen at later times, indicating loss of control by the primed CD8(+) T cells. In the present study, we evaluated CD8(+) T cells in an optimized system, consisting of OTI T-cell-receptor (TCR) transgenic mice, which generate clonal CD8(+) T cells specific for K(b)-SIINFEKL of OVA, and a recombinant γHV68 that expresses OVA (γHV68.OVA). Our aim was to test whether this optimized system would result in more effective control not only of acute infection but also of later forms of latent infection than was seen with previous strategies. First, we show that OTI CD8(+) T cells effectively controlled acute replication of γHV68.OVA in liver, lung, and spleen at 8 and 16 days after infection of OTI/RAG mice, which lack expression of B and CD4(+) T cells. However, we found that, despite eliminating detectable acute replication, the OTI CD8(+) T cells did not prevent the establishment of latency in the OTI/RAG mice. We next evaluated the effectiveness of OTI T cells in OTI/B6 animals, which express B cells—a major site of latency in wild-type mice—and CD4(+) T cells. In OTI/B6 mice OTI CD8(+) T cells not only reduced the frequency of cells that reactivate from latency and the frequency of cells bearing the viral genome at 16 days after infection (similar to what has been reported before) but also were effective at reducing latency at 42 days after infection. Together, these data show that CD8(+) T cells are sufficient, in the absence of B cells and CD4(+) T cells, for effective control of acute replication. The data also demonstrate for the first time that a strong CD8(+) T-cell response can limit long-term latent infection