Activation Of CD8 Lymphocytes Research Articles

Cellular immunodeficiency enhances the progression of human papillomavirus‐associated cervical lesions

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

Serum levels of interleukin 1-?, tumor necrosis factor-?, soluble interleukin 2 receptor and soluble CD8 in seronegative spondylarthropathies

Seronegative spondylarthropathies are disorders with the same predisposing antigen, namely HLA B27, a class I molecule of the HLA system. The mechanisms of the different diseases are unknown, and there is no proof of immune system participation. We have investigated patients with spondylarthropathies in order to search for an immunological component in the pathophysiology of these disorders, by measuring the serum level of two inflammatory cytokines--IL1 beta and TNF alpha--by a radioimmunological assay and the serum level of two soluble T cell activation markers--soluble IL2 receptor and soluble CD8--by an enzyme-linked immunosorbent assay. The choice of soluble CD8 can be explained by the strong link between HLA B27 and spondylarthropathies. Our series compared 24 patients to 24 healthy matched controls. A similar IL1 beta serum level was observed in both groups, while in the patients there was a nonsignificant increase in the TNF alpha level, a significant decrease in the soluble IL2 receptor level and a significant increase in the soluble CD8 serum level. The normal or moderately increased serum IL1 beta and TNF alpha levels in the disease group do not exclude a local role for these cytokines in the synovium or other inflammatory areas. However, we found a higher soluble CD8 serum level in the patient group. Most of these patients were in clinical exacerbation of their disease. As the serum level of soluble CD8 is well correlated with T CD8 lymphocyte activation, our data suggest that this lymphocyte subset is stimulated and consequently probably involved in seronegative spondylarthropathies.

Cyclosporine A and prednisolone inhibit lectin- and alloantigen-induced release of sCD8: Correlation with proliferative responses

It has been shown previously that there is a strong correlation between the in vitro release of soluble CD8 glycoprotein (sCD8) and CD8 + T lymphocyte activation. In the present study, the lectin stimulation of peripheral blood mononuclear cells (PBMC) induced a dose-dependent release of sCD8 which correlated with the magnitude of CD8 lymphocyte activation as measured by the expression of the interleukin 2 (IL-2) receptor and HLA-DR antigen and of the T cell proliferative responses. Both the proliferative responses and the release of sCD8 were inhibited by cyclosporine A (CyA) and prednisolone (PRED) in a concentration-dependent manner. When the immunosuppressants were present for only 60 min before the initiation of the cultures, an inhibitory effect was also seen, but this was maximal only when the agents were added at the initiation of the culture period; when the addition of CyA or PRED was delayed for either 24 or 48 hr after the initiation of the culture, the degree of inhibition of the proliferative response was greatly reduced. However, there was a significant inhibition of sCD8 release by CyA even when it was added 48 hr after the culture initiation. The addition of recombinant IL-2 did not affect the lectin-induced sCD8 release. The inhibition of the lectin-induced proliferative response and sCD8 release by PRED, but not that by CyA, was reversed by the recombinant IL-2. Alloantigen stimulation also induced sCD8 release and this release was inhibited both by CyA and by PRED. These data, together with the known effects of CyA on differentiation, clonal amplification, and activation of CD8 T lymphocytes, suggest that in vitro sCD8 release occurs during the early stages of activation of CD8 + cytotoxic T cells.