CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

Abstract

Three-color flow cytometry immunophenotyping revealed significant increases of CD57 + and CD28 − cells among both circulating CD4 + and CD8 + T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57 + cells among circulating CD4 + T lymphocytes was frequently detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57 + /CD28 − T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-␥, and TNF-␣ than their CD57 − /CD28 + counterparts. Cytotoxic activity of circulating CD8 + T lymphocytes, measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57 + /CD28 − subset. Moreover, a marked cytotoxic activity was detected within CD4 + CD57 + T cells from some B-CLL patients. Finally, the patients' CD57 + /CD28 − T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57 + /CD28 − T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.

Involvement of CD4+,CD57+ T cells in the disease activity of rheumatoid arthritis

“…To date, the cytokine profile of CD57ϩ T cells has been studied both in healthy patients and in patients with various diseases (13,14). However, to our knowledge, there has been no study evaluating cytokine production by CD57ϩ T cells in patients with RA.…”

Principles of adoptive T cell cancer therapy

“…In retrospect, previous clinical trials have primarily tested adoptively transferred populations of CD8 + T EM cells (31). This approach was taken because available tissue culture technologies resulted in rapid differentiation of T cells to late-stage effector cells; latestage T EM cells express CD57 and have poor replicative capacity (32,33). In vitro, T EM cells are superior to T CM cells at tumor cytotoxicity.…”

“…In vitro, the limit of polyclonal expansion for human adult mature CD4 + T cells is about [30][31][32][33][34][35][36][37][38][39][40] doublings of the population size (84,108). In previous studies, we found that human naive CD4 + T cells have telomeres that are, on average, 1.4 kb longer than those of human memory T cells (109).…”

T cells and aging update February 1999

“…To give some examples: the percentage of CD28 + cells decreases during Chagasic progression (391); both CD4 and CD8 cells show decreased CD28 expression in chronic B lymphocytic leukemia (392) and in hairy cell leukaemia (393); in Crohn´s Disease, the ability of CD28 to mediate costimulation of CD4 cells is compromised (394). It may also be interesting to note that in long-term allogeneic kidney graft transplant recipients, decreased CD28 expression correlated with graft survival over extended periods of time (395) and this was accompanied by reduced proliferation in vitro by graft recipent lymphocytes stimulated by donor cells (396).…”

“…The relationship of these CD28-negative cells to ageing as opposed to genetically-influenced autoimmune disease is therefore unclear at present. However, it is clearly not generally the case that CD28-negative cells ex vivo are apoptosis-resistant; for example, in B-CLL and hairy cell leukaemia, the CD28-negative cells while retaining normal functions such as cytotoxicity and cytokine release, show decreased clonal expansion capacity and increased susceptibility to apoptosis (393). The difference therefore may be related to clearly distinct pathological process in autoimmune disease and other situations of chronic antigen stimulation.…”