CD4 and CD8: an inside-out coreceptor model for innate immune cells

Abstract

CD8 and CD4 are expressed by several cell types that do not express TCR. These include DCs, macrophages, monocytes, and NK cells. CD8(+) monocytes and macrophages are abundant at the site of pathology in many rat disease models, particularly those involving immune complex-mediated pathology. Indeed, in some disease models, CD8(+) macrophages correlate with severity of pathology or directly cause pathology or tumor cell killing. Evidence suggests CD8 or CD4 can enhance FcgammaR-dependent responses of human monocytes. Building on data that key components of TCR and FcgammaR signaling can substitute one another efficiently, we postulate that CD4 and CD8 operate with FcgammaR and potentially other receptors to enhance responses of T cells and various innate immune cells. Our model suggests CD8 on myeloid cells may contribute directly to tumor killing and tissue pathology by enhancing FcgammaR responses. Moreover, the model suggests a role for CD8 in cross-presentation of antibody-associated antigen by DCs and a new mechanism to regulate TCR sensitivity.

High Frequencies of Polyfunctional CD8+NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

“…Furthermore, our data emphasize that a better understanding of the precise role of CD8 on human NK cells is required. The surface expression of the homodimer CD8␣␣ on NK cells was observed in rats (47) and pigs (48) but was reported to be absent in mice (49) and thus seems to vary across different mammalian species (50). In rhesus macaques, one of the best-studied nonhuman primate models, virtually all NK cells express CD8 (28,51,52).…”

CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability

“…In relation to our hypothesis that CCR7-competent DCs prevent fibrosis, these data indicate that the expression of CCR7 by DCs indeed prevents fibrosis, but because T cells may be capable of preventing fibrosis as well if they are allowed to appropriately express CCR7, these data are best interpreted as showing that CCR7 + DCs are sufficient for preventing fibrosis, but it is less clear here if the DCs are necessary. One additional caveat in this scenario might be that some DCs express CD4 (23), while some CD8 + T cells express CD11c (24). Lymphatic collecting vessel permeability is controlled by IRF4-dependent DCs.…”

Phenotypic and functional evaluation of CD3+CD4-CD8- T cells in human CD8 immunodeficiency

“…CD8a is also expressed by human monocytes and enhances FcγR-dependent responses. 32 However, in CD8 deficiency T-cell clones that fulfill the functional requirements for intrathymic survival display aberrant phenotypes in the periphery (DN T cells), but seem to be functional. It is, therefore, possible that in human CD8 immunodeficiency the DN cells are in fact MHC class I-restricted, with cytolytic function.…”