In Brief

T cells

CD8⁺ T lymphocyte mobilization to virus-infected tissue requires CD4⁺ T-cell help Nakanishi, Y. et al. Nature 462 510–514 (2009)

Effective priming and maintenance of CD8⁺ T cell responses are known to require 'help' from CD4⁺ T cells, but is help also required during the effector stage? Now, it is shown that effector cytotoxic T lymphocytes (CTLs) do indeed need CD4⁺ T cell help to enter virally infected tissue. Virus-specific CTLs that were primed in the presence of CD4⁺ T cell help and then transferred to mice that lacked CD4⁺ T cells failed to migrate to the site of herpes simplex virus infection in the vaginal mucosa. CTL recruitment was shown to depend on interferon-γ (IFNγ) production by CD4⁺ T cells that entered the vagina 2 days earlier. The IFNγ did not act directly on the CTLs but induced the secretion of CXC-chemokine ligand 9 (CXCL9) and CXCL10 by vaginal tissue cells. These chemokines bind to CXC-chemokine receptor 3 expressed by the CTLs, guiding them to the site of infection.

Innate immunity

Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium Volkman, H. E. et al. Science 10 Dec 2009 (doi: 10.1126/science.1179663)

The immune cell aggregates (granulomas) that form after infection with Mycobacterium spp. were originally thought to be protective by containing the infection; we now know that mycobacteria can direct the formation of granulomas as sites for bacterial proliferation and infection of new cells. Ramakrishnan and colleagues show that Mycobacterium marinum achieves this in zebrafish by inducing the host protein matrix metalloproteinase 9 (MMP9). The secreted M. marinum virulence factor ESAT-6 induces the production of MMP9 by epidermal cells adjacent to the granuloma; in turn, MMP9 recruits additional macrophages to the granuloma. MMP9 activity, the kinetics of granuloma formation and bacterial proliferation were found to be linked. This study provides a mechanistic explanation for the correlation between MMP9 activity and susceptibility to tuberculosis in humans and indicates that MMP9 might be a therapeutic target.

Regulatory T cells

T cell receptor CDR3 sequence but not recognition characteristics distinguish autoreactive effector and Foxp3⁺ regulatory T cells Liu, X. et al. Immunity 10 Dec 2009 (doi: 101.1016/j.immuni.2009.09.023)

This study examined the relationship between effector T cells and regulatory T (T_Reg) cells during an autoimmune response to determine whether T_Reg cells arise from the conversion of effector T cells or the recruitment of a distinct population. In a T cell receptor-α (TCRα)-transgenic model of experimental autoimmune encephalomyelitis (EAE), the effector T cells and T_Reg cells isolated from the central nervous system (CNS) of mice with EAE could be fully distinguished by an acidic versus aliphatic residue at position 4 of the TCRβ complementarity-determining region 3 (CDR3), which shows that they arise from different population reservoirs and argues against their interconversion. In support of conversion being limited, the frequency of shared CDR3 sequences between effector T cells and T_Reg cells was similar in pre-immune splenocytes, post-immune splenocytes and CNS-infiltrating cells.