A T cell activation antigen, Ly6C, induced on CD4+ Th1 cells mediates an inhibitory signal for secretion of IL-2 and proliferation in peripheral immune responses

Abstract

A T cell activation antigen, Ly6C, is considered to be involved in the autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains largely unknown. We prepared a rat anti-mouse Ly6C monoclonal antibody (mAb) (S14) that inhibits the proliferation of peripheral T cells stimulated with anti-CD3 mAb in vitro. S14 mAb, the specificity of which is confirmed by a cDNA transfectant, recognizes Ly6C antigen preferentially expressed on a part of CD8+ T cells in peripheral lymphoid organs. The immunohistochemical analysis demonstrates that Ly6C appears on CD8+ T cells in the conventional T cell-associated area of BALB/c but not of nonobese diabetic (NOD) mice, confirming the absence of Ly6C+ T cells in NOD mice. Addition of soluble S14 mAb to the culture does not influence the proliferation of T cells in vitro; however, the S14 mAb coated on the plate clearly inhibits the proliferation and IL-2 production of anti-CD3-stimulated peripheral T cells. The T cells are arrested at the transitional stage from G0/G1 to S+G2/M phases, but they are not induced to undergo apoptotic changes in vitro. This inhibitory signal provided through the Ly6C molecule inhibited IL-2 secretion in a subpopulation of the activated CD4+ T cells. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the cytokine secretion from Th1 clones is preferentially inhibited. These results suggest that Ly6C mediates an inhibitory signal for secretion of cytokines from Th1 CD4+ T cells, potentially causing the inhibition of immune response in peripheral lymphoid tissues.

Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling

“…Ly6c is 21.1 cM from D15mit229 , and was poorly expressed in NOD thymocytes under all conditions (2.3-fold decrease; Figure 8). This reduced expression has been previously observed to be due to a Ly6c promoter polymorphism in NOD mice, and is thus a known cis effect [65]. Functionally, Ly6c inhibits the signal for secretion of interleukin (IL)2 and proliferation in peripheral CD4 + cells [65], and cross-linking of Ly6c causes clustering of Leukocyte function associated molecule 1 (LFA-1, CD11a/CD18) on the surface of CD8 T cells [66].…”

Dynamic Control of Self-Specific CD8+ T Cell Responses via a Combination of Signals Mediated by Dendritic Cells

“…However, our studies reveal that Ly6C expression is associated with impaired proliferation and lack of differentiation into effector CTL following encounter with peptidepulsed iDC. Other studies have demonstrated that Ly6C expression may also be associated with reduced IL-2 production among CD4 ϩ T cells (28), which as a result, may affect the expression of CD25. Further studies have revealed that there is a deficiency in Ly6C expression among autoimmune susceptible mouse strains such as NOD and NZB (29), suggesting that low levels of Ly6C-expressing CD8 ϩ T cells may also be linked to failure of selftolerance induction.…”

“…We also examined the level of expression of Ly6C, as there is some evidence that expression of Ly6C may be associated with T cell anergy. Furthermore, a deficiency in Ly6C expression has been linked to autoimmunity (28,29). MACS-purified naive Thy1.1 ϩ CL4 CD8 ϩ T cells were labeled with CFSE and cocultured in the presence of iDC or mDC pulsed with K d HA peptide.…”

“…Previous studies have shown that there may be association of Ly6C expression with memory and effector function by T cells (27); however, other studies have suggested that Ly6C is associated with decreased effector function (28). Ly6C may also have a role in tolerance induction, as evidenced by the fact that certain mouse strains that are prone to the autoimmune diseases type 1 diabetes mellitus or systemic lupus erythematosus (NOD and New Zealand Black (NZB), respectively), have a mutation in Ly6C (29).…”

Ly6C expression differentiates plasma cells from other B cell subsets in mice

“…These molecules are found on hematopoietic cells as well as on other cells [12][13][14][15][16], and are all encoded by genes located on chromosome 15 [13]. Ly6C has previously been shown to be expressed on a subset of CD8 + T cells [17] and on NK1.1 + cells [18] representing both CD3 + NKT cells and CD3 -NK cells. Furthermore, Ly6C is expressed on a subset of macrophages [19].…”