CD5 sweetens lymphocyte responses

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Abstract
The cell walls of pathogenic and commensal bacteria and fungi contain a variety of carbohydrate-containing moieties, not produced by animals. The presence of these lipopolysaccharides (LPSs), lipoteichoic acids (LTAs), peptidoglycans (PGNs), and zymosans in host tissues thus alerts the host to invasive bacterial or fungal infections. Several families of pattern recognition receptors (PRRs) expressed by epithelial and phagocytic cells contribute to recognition of microbial cell wall components. These PRRs include toll-like receptors (TLRs), nod-like receptors (NLRs), and scavenger receptors. Cell surface TLRs and cytosolic NLRs respond to microbial components by eliciting production of cytokines and chemokines that activate or amplify host inflammatory and immune responses. In contrast, at least some members of the scavenger-receptor cysteine-rich (SRCR) superfamily contribute more to the resolution of inflammation. In this issue of PNAS, a lymphocyte-expressed SRCR, CD5, is shown to bind the fungal polysaccharide β-glucan (1). Together with a recent study on CD6 (2), this work shows that SRCRs expressed on the lymphocyte cell surface are PRRs that detect diverse microbe-derived carbohydrates. Moreover, previous data implicating CD5 in negative regulation of lymphocyte antigen receptor signaling suggest that ligation of these PRRs with microbial components may profoundly influence lymphocyte activation and autoimmunity (Fig. 1). Potential immunological consequences of pathogen-associated molecular pattern recognition by lymphocyte SRCRs. (A) Preventing autoimmunity. Infection exposes normally cryptic self-ligands that stimulate anergic lymphocytes or lymphocytes with low affinity for self antigens. In the presence of microbial products that signal through CD5 or other SRCRs, the threshold for TCR or BCR signaling is increased and activation of autoreactive lymphocytes is dampened. (B) Tuning of the antimicrobial T cell response. Infection results in presentation of numerous microbial antigens and activation of lymphocytes with multiple distinct specificities. Lymphocytes with the highest reactivity to microbial antigens receive …