Anti-CD6 monoclonal antibody, clone NJM9

Effective CD8(+) T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8(+) T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8(+) T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6(+)PD-1(+)CD8(+) T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6(-)PD-1(+)CD8(+) T cell counterparts. The frequency of CD8(+)PD-1(+) and CD8(+)CD6(-)PD-1(+) T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8(+)CD6(+)PD-1(+) T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6(+)PD-1(+)CD8(+) T-cells expressed elevated levels of SHP2 phosphatase compared to CD6(-)PD-1(+)CD8(+) T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8(+) T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.

A formal description of collective electronic states in condensed-matter systems lacking long-range periodicity remains a theoretical challenge. To experimentally explore the differences in electronic and magnetic behavior between metallic quasicrystals (QCs) and their conventional crystalline analogs [quasicrystal approximants (QCAs)], we have grown single crystals of Y1-xGdx-Cd6 (QCA) together with their QC counterparts i-Y1-xGdx-Cd for x = 0.006, 0.01, 0.1, and 1.00, and we carried out comparative T-dependent electron spin resonance (ESR) measurements. On the high Gd concentration side, x = 1.00, we confirm that GdCd6 adopts an antiferromagnetic ground state below T-N similar to 22 K, whereas i-Gd-Cd presents spin-glass-like behavior showing similar local and dynamical properties from the point of view of ESR. For the diluted samples, our ESR experimental results show similar local conduction electron polarization behavior at the Gd3+ site in all QC/QCA pairs investigated, supporting the validity of using QCAs as periodic representations of QCs in terms of short-range electronic interactions. However, there is a measurable difference in the Korringa relaxation rate (spin-flip relaxation process between the localized Gd3+ 4f electron and the delocalized s-type conduction electrons at the Fermi surface) between the QC/QCA pairs probably associated with the lack of periodicity. We expect that our comparative ESR study may provide support and motivation for the development of new theoretical approaches toward a generalized band-structure theory, contemplating condensed-matter systems beyond the scope of traditional periodicity.