Estudo dos repertórios de receptores killer nas células natural Killer e nos linfócitos T do sangue periférico de indivíduos adultos normais

Abstract

Cell mediated cytotoxicity has a key role in both adaptive and innate immune responses, especially in the elimination of tumour cells, as well as virus infected cells. Not only Natural Killer (NK) cells are implicated in this complex process, but also cytotoxic T lymphocytes (CTL). NK-cells are phenotypically characterized by the absence of the CD3/TCR (T Cell Receptor) complex, and by the expression of CD16 and/or CD56 on the cell membrane. Two NK-cell populations can be distinguished in the peripheral blood of a normal individual: CD56+ NK-cells, expressing lower levels of CD56 and being CD16+, that represent 90-95% of circulating NK-cells and have a more powerful cytotoxic activity; and CD56++ NK-cells, having higher levels of CD56 and expressing partially or not expressing at all CD16, that are mainly involved in immune regulatory functions. NK-cells have a crucial role in eliminating target cells. In this process, proteins such as granzymes and perforins, that are constitutively stored in their cytoplasmatic granules, are released. As NK-cells, a small portion of peripheral blood T-cells express the CD56 adhesion molecule, and these cells are mainly CTL. CTL are phenotypically a heterogeneous population with some common characteristics. Unlike NK-cells, CTL express the CD3/TCR complex. However the CTL and NK-cells are in many ways similar. For instance, they share a number of cell surface receptors and both have cytoplasmatic cytotoxic granules. The cytotoxic activity displayed by NK-cells and CTL results from a balance between positive and negative signals transmitted by activator and inhibitor receptors, generally known as killer receptors. In this study the expression of several types of killer receptors on NK-cells and T-cells in peripheral blood of 30 healthy adults was analyzed and the expression of these receptors in different subpopulations was characterized: CD56+ and CD56++ NK-cells, and CD56- and CD56+ T-cells. The evaluation of the expression of killer receptors on normal NK-cells and T-cells is important when we consider the immunophenotypic study of hemato-oncological diseases, once we set out the base line for identification of aberrant phenotypes expressed by neoplastic NK-cells and T-cells. In addition, the establishment of normal values is crucial to better understand the mechanisms underlying autoimmune disorders, transplant rejection, as well as the immune responses to viruses and tumours

Date of Award	Dec 2011
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Margarida Lima (Supervisor)