Expression of TIA-1 and TIA-2 in T cell malignancies and T cell lymphocytosis.

Abstract

Objective-To investigate the reactivity with TIA-1 and TIA-2, two monoclonal antibodies that recognise, respectively, granular structures in T lymphocytes and the T cell receptor chain in cells from a variety of T cell disorders. Methods-Cytoplasmic staining with TIA-1 and TIA-2 was carried out by the immunoalkaline phosphatase anti-alkaline phosphatase technique in 67 cases with a T cell disorder: 31 large granular lymphocyte (LGL) leukaemia, nine T-prolymphocytic leukaemia (T-PLL), five Sezary syndrome, four peripheral T cell lymphoma (PTCL), 13 T cell lymphocytosis, and five T-acute lymphoblastic leukaemia (T-ALL). All had over 75% abnormal T cells which were CD2+, CD3+, CD5+, CD7+, and negative with B cell markers.Results-TIA-1 was positive in 77% cases of LGL leukaemia and half of the PTCL and T-ALL, whereas it was negative in all Sezary syndrome and most T-PLL (8/9) and reactive T-lymphocytosis (10/13). In LGL leukaemia, TIA-1 was positive irrespective of the membrane phenotype, whether CD8 +, CD4-or CD4 +, CD8-, and was more often positive in cases where cells were CD16+, CD56+, or CD57+. TIA-2 was positive in 60% of cases encompassing all diagnostic types of T cell disorder. There was no correlation between TIA-2 expression and that of other T cell markers, activation antigens, and natural killer markers. Conclusions-The pattern of TIA-1 expression in T cell malignancies may help in the differential diagnosis among LGL leukaemia (high expression), T cell lymphocytosis and other T cell diseases (low expression). As TIA-2 is expressed in over 95% mature T lymphocytes and thymic cells, its assessment may be usefiu to demonstrate aberrant phenotypes which can be exploited for detecting minimal residual disease. (J Clin Pathol 1996;49:154-158)

Leukemic CD3+ LGL share functional properties with their CD8+CD57+ cell counterpart expanded after BMT

“…The CD3 responsiveness we describe goes hand in hand with the rapid Ca 2+ mobilization in single cell LGL upon interaction with its target cell, 43 and makes it conceivable that anti-CD3 MoAb triggers an intracellular signal resulting in phosphorylation of already expressed LFA-1 whose role in such activated conformation is necessary for target binding. 44 Furthermore, this CD3-triggered lysis is in line with previous reports describing leukemic LGL as positive cells for perforin and TiA-1, specific molecules of T lymphocyte granular structures 7,8 and for FasL, a marker of activated cells. 10,11 Of note, these leukemic cells also produce IFN-␥ after CD3 activation; so do LGL cell lines derived from the tail tumors of transgenic mice for Tax protein.…”

“…3 As T-LGL expansions can display an heterogeneous phenotype, [4][5][6] in this report we will focus on the non-aggressive and most frequent CD3 + CD16 + CD57 + T-LGL leukemia, ie negative for CD56 and positive for CD8. 3 Perforin, a cytolytic molecule responsible for pore formation in target cells, and TiA-1, a membrane protein from cyto- lytic granules, were both present in several cases of T-LGL leukemia 7,8 suggesting a lytic potential. Furthermore, FasL, predominantly expressed on and secreted by activated T cells, 9 is constitutively expressed by these leukemic cells and sera from LGL leukemic patients contain detectable levels of sFasL, while sera from healthy persons do not.…”

How I treat prolymphocytic leukemia

“…CD52 is expressed at high density, explaining to some degree the in vivo sensitivity to the anti-CD52 monoclonal antibody alemtuzumab. 10 Cell surface antigens linked to T-cell activation, such as CD25, CD38, and class II HLA-DR, may be variably expressed, but markers identifying cytotoxic T cells, such as TIA-1, are negative, even in cases with a CD8 ϩ phenotype 11 Genetics. Recurrent chromosomal abnormalities involving chromosome 14 are present in almost 75% of T-PLL cases, with inversion 14 being the commonest ( Figure 4A).…”

“…SOX 11 has high sensitivity for MCL, being positive in more than 90% of cases, including those negative for cyclin D1. 55 It is negative in most other mature B-cell malignancies tested, but expression can be seen, independent of t (11,14), in up to 50% of cases of HCL and Burkitt lymphoma. 56 We have documented mutations of the TP53 gene in more than 50% of the B-PLL cases.…”

Sezary cell-like leukemia with atypical immunophenotype

“…syndrome. 9 The clinical course in Sezary cell-like leukemias is usually aggressive 2,11,12,13 and only one case treated with aggressive Molecular analysis chemotherapy and bone marrow transplantation 3 had a proThis was performed on bone marrow sections applying a polymerase chain reaction (PCR) and using specific primers to the beta and gamma chain genes of the T cell receptor (TCR) as previously described. 10 …”